TY - JOUR. T1 - Analysis of a mutant amino acid-activating domain of surfactin synthetase bearing a serine-to-alanine substitution at the site of carboxylthioester formation. AU - Vollenbroich, Dirk. AU - Kluge, Britta. AU - DSouza, Cletus. AU - Zuber, Peter. AU - Vater, Joachim. PY - 1993/7/5. Y1 - 1993/7/5. N2 - The reactive serine of the TGGHSL thioester binding motif of the first amino acid-activating domain of surfactin synthetase was replaced by alanine using site-directed mutagenesis. The multienzyme from cells of the resulting mutant lost its ability for thioester formation with l-Glu and was therefore inactive in surfactin production. The thiolation reactions catalyzed by the other amino acid-activating domains of surfactin synthetase were not affected by the mutation. The results show that l-Glu is acativated at the first domain of surfactin synthetase, and give further evidence that a serine residue is essential for substrate amino acid activation at the reaction centers of peptide ...

Adenylation domains of non-ribosomal peptide synthetases (NRPS) catalyse the formation of aminoacyl adenylates, and in addition synthesize mono- and dinucleoside polyphosphates. Here, we show that NRPS systems furthermore contain an ATPase activity in the range of up to 2 P(i)/min. The hydrolysis rate by apo-tyrocidine synthetase 1 (apo-TY1) is enhanced in the presence of non-cognate amino acid substrates, correlating well with their structural features and the diminishing adenylation efficiency. A comparative analysis of the functional relevance of an analogous sequence motif in P-type ATPases and adenylate kinases (AK) allowed a putative assignment of the invariant aspartate residue from the TGDLA(V)R(K) core sequence in NRPS as the Mg(2+) binding site. Less pronounced variations in ATPase activity are observed in domains with relaxed amino acid specificity of gramicidin S synthetase 2 (GS2) and delta-(L-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS), known to produce a set of ...

TY - JOUR. T1 - Dynamic thiolation-thioesterase structure of a non-ribosomal peptide synthetase. AU - Frueh, Dominique P.. AU - Arthanari, Haribabu. AU - Koglin, Alexander. AU - Vosburg, David A.. AU - Bennett, Andrew E.. AU - Walsh, Christopher T.. AU - Wagner, Gerhard. PY - 2008/8/14. Y1 - 2008/8/14. N2 - Non-ribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) produce numerous secondary metabolites with various therapeutic/antibiotic properties. Like fatty acid synthases (FAS), these enzymes are organized in modular assembly lines in which each module, made of conserved domains, incorporates a given monomer unit into the growing chain. Knowledge about domain or module interactions may enable reengineering of this assembly line enzymatic organization and open avenues for the design of new bioactive compounds with improved therapeutic properties. So far, little structural information has been available on how the domains interact and communicate. This may be because of inherent ...

The tubulin tyrosination/detyrosination cycle is a well-established posttranslational modification, which is carried out by two enzymes: Tubulin Tyrosine Ligase (TTL) and Tubulin Tyrosine Carboxypeptidase (TTCP). In this paper, I present evidence suggesting that the cycle itself is under the hierarc …

Fungi have a high impact on our society both in a negative and positive way, due to the ability to produce secondary metabolites. Non-ribosomal peptide synthetases (NRPSs) are multi-modular enzymes responsible for the synthesis of some of these compounds by a mechanism of action which bypasses the ribosomal machinery. These compounds are of a great value due to their bioactive properties, as for example, the cytotoxicity displayed towards some cancer cell lines. Therefore, NRPSs and their products are important targets of study ...

Nonribosomal peptides (NRP) are a class of peptide secondary metabolites, usually produced by microorganisms like bacteria and fungi. Nonribosomal peptides are also found in higher organisms, such as nudibranchs, but are thought to be made by bacteria inside these organisms. While there exist a wide range of peptides that are not synthesized by ribosomes, the term nonribosomal peptide typically refers to a very specific set of these as discussed in this article. Nonribosomal peptides are synthesized by nonribosomal peptide synthetases, which, unlike the ribosomes, are independent of messenger RNA. Each nonribosomal peptide synthetase can synthesize only one type of peptide. Nonribosomal peptides often have cyclic and/or branched structures, can contain non-proteinogenic amino acids including D-amino acids, carry modifications like N-methyl and N-formyl groups, or are glycosylated, acylated, halogenated, or hydroxylated. Cyclization of amino acids against the peptide backbone is often ...

ID FOLE_YEAST Reviewed; 548 AA. AC Q08645; D6W2U3; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 1. DT 25-OCT-2017, entry version 157. DE RecName: Full=Folylpolyglutamate synthase; DE EC=6.3.2.17; DE AltName: Full=Folylpoly-gamma-glutamate synthetase; DE Short=FPGS; DE AltName: Full=Tetrahydrofolylpolyglutamate synthase; DE Short=Tetrahydrofolate synthase; GN Name=MET7; Synonyms=MET23; OrderedLocusNames=YOR241W; ORFNames=O5248; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Bakers yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; OC Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 96604 / S288c / FY1679; RX PubMed=8972580; RX DOI=10.1002/(SICI)1097-0061(199612)12:15,1575::AID-YEA45>3.0.CO;2-E; RA Boyer J., Michaux G., Fairhead C., Gaillon L., Dujon B.; RT Sequence and analysis of a 26.9 kb fragment from chromosome XV of ...

cansSAR 3D Structure of 3COY_A | CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS PANTOTHENATE SYNTHETASE AT 2.05 ANG RESOLUTION- IN COMPLEX WITH SULPHONAMIDE INHIBITOR 3 | 3COY

Nocardia brasiliensis genes for two putative non-ribosomal peptide synthetases, hypothetical protein, putative condensation domain protein, putative thioesterase, putative polyketide synthase, putative thioesterase, putative dehydrogenase, putative non-ribosomal peptide synthetase, complete cds, strain: NBRC ...

Polyketide synthase (PKSs) and nonribosomal peptide synthetase (NRPSs) are large multimodular enzymes involved in biosynthesis of polyketide and peptide toxins produced by fungi. Furthermore, hybrid enzymes, in which a reducing PKS region is fused to a single NRPS module, are also responsible of the synthesis of peptide-polyketide metabolites in fungi. The genes encoding for PKSs and NRPSs have been exposed to complex evolutionary mechanisms, which have determined the great number and diversity of metabolites. In this study, we considered the most important polyketide and peptide mycotoxins and, for the first time, a phylogenetic analysis of both PKSs and NRPSs involved in their biosynthesis was assessed using two domains for each enzyme: β-ketosynthase (KS) and acyl-transferase (AT) for PKSs; adenylation (A) and condensation (C) for NRPSs. The analysis of both KS and AT domains confirmed the differentiation of the three classes of highly, partially and non-reducing PKSs. Hybrid PKS-NRPSs involved in

Considering that 70% of our planets surface is covered by oceans, it is likely that undiscovered biodiversity is still enormous. A large portion of marine biodiversity consists of microbiomes. They are very attractive targets of bioprospecting because they are able to produce a vast repertoire of secondary metabolites in order to adapt in diverse environments. In many cases secondary metabolites of pharmaceutical and biotechnological interest such as nonribosomal peptides (NRPs) and polyketides (PKs) are synthesized by multimodular enzymes named nonribosomal peptide synthetases (NRPSes) and type-I polyketide synthases (PKSes-I), respectively. Novel findings regarding the mechanisms underlying NRPS and PKS evolution demonstrate how microorganisms could leverage their metabolic potential. Moreover, these findings could facilitate synthetic biology approaches leading to novel bioactive compounds. Ongoing advances in bioinformatics and next-generation sequencing (NGS) technologies are driving the ...

The selective degradation of many proteins in eukaryotic cells is carried out by the ubiquitin system. In this pathway, proteins are targeted for degradation by covalent ligation to ubiquitin, a highly conserved protein [1]. Ubiquitylated proteins were degraded by the 26S protea-some in an ATP-depended manner. The degradation of ubiquitylated proteins were controlled by isopeptidase cleavage. A well characterised system of ubiquitylation and deubiquitylation is the calmodulin system in vitro [2]. Detection of ubiquityl-calmodulin conjugtates in vivo have not been shown so far. In this article we discuss the detection of ubiquitin calmodulin conjugates in vivo by incubation with a novel high-molecular weight ubiquitylprotein-isopeptidase in rabbit tissues. Proteins with a molecular weight of ubiquityl-calmodulin conjugates could be detected in all organs tested. Incubation with ubiquitylprotein-isopeptidase showed clearly a decrease of ubiquitin calmodulin conjugates in vivo with an origination of

Background: Folylpolyglutamate synthetase (FPGS), an important enzyme in the folate metabolic pathway,plays a central role in intracellular accumulation of folate and antifolate in several mammalian cell types. Loss ofFPGS activity results in decreased cellular levels of antifolates and consequently to polyglutamatable antifolatesin acute lymphoblastic leukemia (ALL). Materials and Methods: During May 1997 and December 2003, 134children diagnosed with ALL were recruited from one hospital in Thailand. We performed a mutation analysis inthe coding regions of the FPGS gene and the association between single nucleotide polymorphisms (SNPs) withinFPGS in a case-control sample of childhood ALL patients. Mutation screening was conducted by polymerasechain reaction-single strand conformation polymorphism (PCR-SSCP) and subsequently with direct sequencing(n=72). Association analysis between common FPGS variants and ALL risk was done in 98 childhood ALL casesand 95 healthy volunteers recruited as controls.

bsk:BCA52141_I3153 K01921 D-alanine-D-alanine ligase [EC:6.3.2.4] , (GenBank) D-alanine-D-alanine ligase A (A) MASGKMRIVVLFGGRSAEHDVSVLSATNVMNALDPAKYEAVPVFVTRAGQWLLSRFVNGA LEKPSSGAELCLVPGGCGRAIVVPDAGAPYEADKIDIIFPVLHGLHGEDGAVQGLAQVAR VPLAGCGIPGSANALDKDIAKRLVNEAGLSTAKSVTITREEVPAFSALEQALGLPIFIKP ARQGSSVGVHKVVTEADYQAAMSDGFTYDDKLLAEEFIQAREVECGVLEDEGGALFVSRA GEIVPAESHCFYSYDAKYIDADGTEIKVPAELPEQVENEIRAIATRAFRVLGCDSMARVD FFVTADRRIVLNEINTIPGFTDMSMYSKVMAVSGVSYPEIINRLVAHGLARGS ...

A set of multienzymes (peptide synthase CepA, CepB, and CepC) are responsible for assembling the heptapeptide. (Figure 2). The organization of CepA, CepB, and Cep C closely resembles other peptide synthases such as those for surfactin (SrfA1, SrfA2, and SrfA3) and gramicidin (GrsA and GrsB).[28] Each peptide synthase activates codes for various amino acids to activate each domain. CepA codes for modules 1, 2, and 3. CepB codes for modules 4, 5, and 6, and CepC codes for module 7. The three peptide synthases are located at the start of the region of the bacterial genome linked with antibiotic biosynthesis, and spans 27 kb.[28] After the linear heptapeptide molecule is synthesized, vancomycin has to undergo further modifications, such as oxidative cross-linking and glycosylation, in trans[clarification needed] by distinct enzymes, referred to as tailoring enzymes, to become biologically active (Figure 3). To convert the linear heptapeptide, eight enzymes, open reading frames (ORFs) 7, 8, 9, 10, ...

A set of multienzymes (peptide synthase CepA, CepB, and CepC) are responsible for assembling the heptapeptide. (Figure 2). The organization of CepA, CepB, and Cep C closely resembles other peptide synthases such as those for surfactin (SrfA1, SrfA2, and SrfA3) and gramicidin (GrsA and GrsB).[41] Each peptide synthase activates codes for various amino acids to activate each domain. CepA codes for modules 1, 2, and 3. CepB codes for modules 4, 5, and 6, and CepC codes for module 7. The three peptide synthases are located at the start of the region of the bacterial genome linked with antibiotic biosynthesis, and span 27 kb.[41]. After the linear heptapeptide molecule is synthesized, vancomycin has to undergo further modifications, such as oxidative cross-linking and glycosylation, in trans[clarification needed] by distinct enzymes, referred to as tailoring enzymes, to become biologically active (Figure 3). To convert the linear heptapeptide, eight enzymes, open reading frames (ORFs) 7, 8, 9, 10, ...

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1N2J: Crystal structures of a pantothenate synthetase from M. tuberculosis and its complexes with substrates and a reaction intermediate

TY - JOUR. T1 - Prediction of substrate-specific pockets in cyclosporin synthetase. AU - Husi, Holger. AU - Schörgendorfer, Kurt. AU - Stempfer, Günter. AU - Taylor, Paul. AU - Walkinshaw, Malcolm D.. PY - 1997/9/1. Y1 - 1997/9/1. N2 - Amino acid sequence comparisons between domains of cyclosporin synthetase have been used to identify regions of the sequence which are responsible for the recognition and binding of the individual amino acids. Using a limited set of selection rules it was possible to identify three amino acid positions in the subdomain sequences which are responsible for amino acid specificity. Homology with the firefly luciferase protein shows that these three key residues are close to each other and line the surface of a putative specific substrate binding pocket located on the amino acyl-adenylation subdomain. These results allow us to predict a large number of cyclosporin synthetase mutants which could be used to synthesise alternative cyclosporin-like peptides.. AB - Amino ...

1N2H: Crystal structures of a pantothenate synthetase from M. tuberculosis and its complexes with substrates and a reaction intermediate

Nonribosomal peptides represent a large variety of natural active compounds produced by microorganisms. Due to their specific biosynthesis pathway through large assembly lines called NonRibosomal Peptide Synthetases (NRPSs), they often display complex structures with cycles and branches. Moreover they often contain non proteogenic or modified monomers, such as the D-monomers produced by epimerization. We investigate here some sequence specificities of the condensation (C) and epimerization (E) domains of NRPS that can be used to predict the possible isomeric state (D or L) of each monomer in a putative peptide. We show that C-and E-domains can be divided into 2 sub-regions called Up-Seq and Down-Seq. The Up-Seq region corresponds to an InterPro domain (IPR001242) and is shared by C-and E-domains. The Down-Seq region is specific to the enzymatic activity of the domain. Amino-acid signatures (represented as sequence logos) previously described for complete C-and E-domains have been restricted to the Down

Harnessing the modular architecture of non-ribosomal peptide synthetases for combinatorial biosynthesis is a longstanding goal in chemical biology. Several recent reports illustrate how computational design and directed evolution can be used to tailor the specificity of these assembly-line enzymes.. ...

K01921 D-alanine-D-alanine ligase [EC:6.3.2.4] , (GenBank) ddl; D-alanine--D-alanine ligase (D-alanylalanine synthetase; D-Ala-D-Ala ligase ...

D-alanine--D-alanine ligase B (D-alanylalanine synthetaseB) (D-Ala-D-Ala ligase B); K01921 D-alanine-D-alanine ligase [EC:6.3.2.4] ...

2002). Many members of this genus of Gram-positive, soil-dwelling bacteria have atypically large genes (>10 kb in size) encoding multimodular polyketide synthases and nonribosomal peptide synthetases that catalyze the biosynthesis of polyketide and nonribosomal peptide antibiotics, respectively (Bentley et al., 2002). The expression of the extraordinarily large genes encoding these mega-enzymes has long been a curiosity (Lipmann et al., 1971; Schwarzer et al., 2003). Three of the largest genes in. the S. coelicolor genome encode the nonribosomal peptide synthetases CDA PSI, CDA PSII, and CDA PSIII (Bentley et al., 2002). The cdaPSI gene (SCO3230) is the largest gene in S. coelicolor at 22 391 bp (Bentley et al., 2002). cdaPSII (SCO3231) and cdaPSIII (SCO3232) are 11 012 and 7253 bp in size, respectively (Bentley et al., 2002; http://strepdb.streptomyces.org.uk). Selleck Ceritinib The megaenzymes encoded by these genes catalyze the biosynthesis. of a cyclic lipopeptide called the ...

Data Availability StatementThe revised coding sequences of are deposited in GenBank under accession quantities KX281943, KX281944, and KX281945, respectively. variety of supplementary metabolite biosynthetic enzymes, including 12 sesquiterpene synthases (STSs), one non-ribosomal peptide synthetase (NRPS), and a polyketide synthase (PKS) [6]. These enzymes are necessary for the biosynthesis of sesquiterpenes, non-ribosomal peptides, and polyketides, respectively. Included in this, six supplementary metabolite gene clusters harbouring genes encoding four STS genes and one each of NRPS and PKS had been also found expressing at notable amounts in the sclerotium [7]. Genome mining provides emerged being a potential avenue to gain access to the chemical variety encoded in basidiomycete fungal genomes [10]. The large numbers of STS genes in the genome features the potential of in making diverse sesquiterpenoids. Many sesquiterpenoids possess powerful antibiotic and cytotoxic actions because of their ...

Cyclodipeptides (CDP) represent a diverse family of small, highly stable, cyclic peptides that are produced as secondary functional metabolites or side products of protein metabolism by bacteria, fungi, and animals. They are widespread in nature, and exhibit a broad variety of biological and pharmacological activities. CDP synthases (CDPSs) and non-ribosomal peptide synthetases (NRPSs) catalyze the biosynthesis of the CDP core structure, which is further modified by tailoring enzymes often associated with CDP biosynthetic gene clusters. In this review, we provide a comprehensive summary of CDP biosynthetic pathways and modifying enzymes. We also discuss the biological properties of some known CDPs and their possible applications in metabolic engineering.

Collectively, given its sensitivity with low cell numbers and avoidance of radioactive substrates, UHPLC-MS/MS-based analysis of FPGS activity may be eligible for routine therapeutic drug monitoring of MTX in RA and leukemia for therapy (non)response evaluations.

Biosynthetic modification of nonribosomal peptide backbones represents a potentially powerful strategy to modulate the structure and properties of an important class of therapeutics. Using a high-throughput assay for catalytic activity, we show here that an L-Phe-specific module of an archetypal nonribosomal peptide synthetase can be reprogrammed to accept and process the backbone-modified amino acid (S)-β-Phe with near-native specificity and efficiency. A co-crystal structure with a non-hydrolysable aminoacyl-AMP analogue reveals the origins of the 40,000-fold α/β-specificity switch, illuminating subtle but precise remodelling of the active site. When the engineered catalyst was paired with downstream module(s), (S)-β-Phe-containing peptides were produced at preparative scale in vitro (~1 mmol) and high titres in vivo (~100 mg l-1), highlighting the potential of biosynthetic pathway engineering for the construction of novel nonribosomal β-frameworks.. ...

Possible in vitro repair of viral RNA by ligase-like enzyme(s) in poliovirus-infected cells.: A soluble polymerase-template complex prepared from poliovirus-inf

Cyanobacteria are an ancient lineage of photosynthetic bacteria from which hundreds of natural products have been described, including many notorious toxins but also potent natural products of interest to the pharmaceutical and biotechnological industries. Many of these compounds are the products of non-ribosomal peptide synthetase (NRPS) or polyketide synthase (PKS) pathways. However, current understanding of the diversification of these pathways is largely based on the chemical structure of the bioactive compounds, while the evolutionary forces driving their remarkable chemical diversity are poorly understood. We carried out a phylum-wide investigation of genetic diversification of the cyanobacterial NRPS and PKS pathways for the production of bioactive compounds. 452 NRPS and PKS gene clusters were identified from 89 cyanobacterial genomes, revealing a clear burst in late-branching lineages. Our genomic analysis further grouped the clusters into 286 highly diversified cluster families (CF) of ...

Gene target information for TTLL10 - tubulin tyrosine ligase like 10 (human). Find diseases associated with this biological target and compounds tested against it in bioassay experiments.

Non-ribosomally synthesized peptides have compelling biological activities ranging from antimicrobial to immunosuppressive and from cytostatic to antitumor. The broad spectrum of applications in modern medicine is reflected in the great structural diversity of these natural products. They contain unique building blocks, such as D-amino acids, fatty acids, sugar moieties, and heterocyclic elements, as well as halogenated, methylated, and formylated residues. In the past decades, significant progress has been made toward the understanding of the biosynthesis of these secondary metabolites by nonribosomal peptide synthetases (NRPSs) and their associated tailoring enzymes. Guided by this knowledge, researchers genetically redesigned the NRPS template to synthesize new peptide products. Moreover, chemoenzymatic strategies were developed to rationally engineer nonribosomal peptides products in order to increase or alter their bioactivities. Specifically, chemical synthesis combined with peptide ...

The polyketide epothilone is a potential anticancer agent that stabilizes microtubules in a similar manner to Taxol. The gene cluster responsible for epothilone biosynthesis in the myxobacteriumSorangium cellulosum was cloned and completely sequenced. It encodes six multifunctional proteins composed of a loading module, one nonribosomal peptide synthetase module, eight polyketide synthase modules, and a P450 epoxidase that converts desoxyepothilone into epothilone. Concomitant expression of these genes in the actinomyceteStreptomyces coelicolor produced epothilones A and B.Streptomyces coelicolor is more amenable to strain improvement and grows about 10-fold as rapidly as the natural producer, so this heterologous expression system portends a plentiful supply of this important agent. ...

TY - JOUR. T1 - Folic acid pathway single nucleotide polymorphisms associated with methotrexate significant adverse events in United States veterans with rheumatoid arthritis. AU - Davis, Lisa A.. AU - Polk, Brooke. AU - Mann, Alyse. AU - Wolff, Roger K.. AU - Kerr, Gail S.. AU - Reimold, Andreas M.. AU - Cannon, Grant W.. AU - Mikuls, Ted R.. AU - Caplan, Liron. PY - 2014/1/1. Y1 - 2014/1/1. N2 - Objective: Methotrexate (MTX) is the cornerstone medication in the treatment of rheumatoid arthritis (RA). We examined whether single nucleotide polymorphisms (SNPs) in enzymes of the folic acid pathway (folylpoly-gamma-glutamate synthetase [FPGS], gamma-glutamyl hydrolase [GGH], and methylenetetrahydrofolate reductase [MTHFR]) associate with significant adverse events (SigAE). Methods: Patients (n=319) enrolled in the Veterans Affairs RA (VARA) registry taking MTX were genotyped for HLA-DRB1-SE and the following SNPs: FPGS (rs7033913, rs10760503, rs10106), GGH (12548933, rs7010484, rs4617146, ...

Catalytic subunit of the neuronal tubulin polyglutamylase complex. Modifies alpha- and beta-tubulin, generating side chains of glutamate on the gamma-carboxyl groups of specific glutamate residues within the C-terminal tail of alpha- and beta-tubulin.

Semantic Scholar extracted view of Further studies of the D-aspartic acid-activating enzyme of Streptococcus faecalis and its attachment to the membrane. by W. L. Staudenbauer et al.

Creating designer molecules using a combination of select domains from polyketide synthases and/or nonribosomal peptide synthetases (NRPS) continues to be a synthetic goal. However, an incomplete understanding of how protein-protein interactions and dynamics affect each of the domain functions stands as a major obstacle in the field. Of particular interest is understanding the basis for a class of methyltransferase domains (MT) that are found embedded within the adenylation domain (A) of fungal NRPS systems instead of in an end-to-end architecture. The MT domain from bassianolide synthetase (BSLS) was removed and the truncated enzyme BSLS-ΔMT was recombinantly expressed. The biosynthesis of bassianolide was abolished and N-desmethylbassianolide was produced in low yields. Co-expression of BSLS-ΔMT with standalone MT did not recover bassianolide biosynthesis. In order to address the functional implications of the protein insertion, we characterized the N-methyltransferase activity of the MT domain as

Catalyzes the decarboxylation of 4-phosphopantothenoylcysteine to 4-phosphopantetheine, a key step in coenzyme A biosynthesis. Involved in salt and osmotic tolerance, and light-regulated plant growth. Trimerization of HAL3 recruits and activates the E3 ubiquitin-protein ligase HIP1, which leads to the degradation of cell cycle suppressors, resulting in enhancement of cell division and plant growth. HAL3 function in cell division seems to be independent from its PPC decarboxylase activity.

Amino acid esters are a group of structurally diverse natural products with distinct activities. Some are synthesized through an inter-molecular esterification step catalysed by nonribosomal peptide synthetase (NRPS). In bacteria, the formation of the intra-molecular ester bond is usually catalysed by a thioesteras

Although numerous marine bacteria are known to produce antibiotics via hybrid NRPS-PKS gene clusters, none have been previously described in

The glycopeptide antibiotics (GPAs) are a structurally complex and medically important class of peptide natural products that include the clinical antibiotics vancomycin and teicoplanin. They contain a large number of non-proteinogenic amino acids and are produced by a linear non-ribosomal peptide synthetase (NRPS) machinery comprising seven modules. Furthermore, GPAs are extensively crosslinked late in their biosynthesis on the NRPS assembly line by the actions of a cascade of Cytochrome P450 enzymes, a process which contributes to the rigidity and structural complexity of these compounds. Due to the challenge of synthesising GPAs, biosynthesis remains the only means of accessing GPAs for clinical use, which makes understanding the biosynthesis of GPAs of key importance. In this presentation, I will detail results from our studies into the NRPS machinery, the P450-catalysed cyclisation cascade and the interplay of these two important biosynthetic processes during GPA biosynthesis. This includes ...

Oxidative phenol cross-linking reactions play a key role in the biosynthesis of glycopeptide antibiotics such as vancomycin. The vancomycin aglycone contains three cross-links between aromatic amino acid side-chains, which stabilize the folded backbone conformation required for binding to the target D-Ala-D-Ala dipeptide. At least the first cross-link is introduced into a peptide precursor whilst it is still bound as a thioester to a peptide carrier protein (PCP) domain (also called a thiolation domain) within the nonribosomal peptide synthetase. We described here methods for the solid-phase synthesis of peptides and their coupling to PCP domains, which may be useful for in vitro studies of cross-linking and related tailoring reactions during nonribosomal glycopeptide antibiotic biosynthesis. ...

Polyglutamase which preferentially modifies alpha-tubulin. Involved in the side-chain elongation step of the polyglutamylation reaction rather than in the initiation step (By similarity). Required for CCSAP localization to both spindle and cilia microtubules (PubMed:22493317). Generates long side-chains (By similarity ...

Peptide synthetases and acyl‐CoA‐synthetases form acyl adenylates which are transferred to CoA or enzyme‐bound pantetheine. To verify the existence of an adenylate domain in peptide synthetases, a 60.8 kDa fragment of tyrocidine 1‐synthetase was constructed by a 1629 bp deletion, expressed in Escherichia coli, and characterized. The truncated multienzyme activated phenylalanine and substrate analogues with comparable kinetics as the over‐expressed synthetase, as judged by ATP‐[32P]PPi exchange reaction. Thus the N‐terminal domain resembling an acyl‐CoA‐synthetase is an autonomous structural element. This N‐terminal domain is followed by a cofactor binding domain, resembling acyl carrier proteins involved in polyketide formation.

Eisendle, M., Oberegger, H., Zadra, I. and Haas, H. (2003) The Siderophore System Is Essential for Viability of Aspergillus nidulans Functional Analysis of Two Genes Encoding L-Ornithine N5-Monooxygenase (sidA) and a Non-Ribosomal Peptide Synthetase (sidC). Molecular Microbiology, 49, 359-375.

Novel way of studying cancer may inspire new treatments. Many of the newest weapons in the war on cancer come in the form of personalized therapies that can target specific changes in an individuals tumor. By disrupting molecular processes in tumor cells, these drugs can keep the tumor from growing and spreading. At the forefront of this work are Binghamton University researchers, Susan Bane, and Susannah Gal, who are deploying a new tool in their study of an enzyme called tubulin tyrosine ligase, or TTL.. In developing these targeted therapies, scientists need to understand exactly what kind of activities within a tumor cell these drugs disturb. Bane, a professor of organic and biological chemistry, and Gal, an associate professor of biological sciences, are getting an insiders look at these cells and paying particular interest to the many cancer cells that contain less-than-normal levels of TTL.. Funded by the National Institute of General Medical Sciences, Bane and Gals work focuses on ...

D-alanine:D-alanine ligase (DDl) is an essential enzyme in bacterial cell wall biosynthesis and an important target for developing new antibiotics. It catalyzes the formation of D-alanine:D-alanine dipeptide, sequentially by using one D-alanine and one ATP as substrates for the first-half reaction, and a second D-alanine substrate to complete the reaction. Some gain of function DDl mutants can use an alternate second substrate, causing resistance to vancomycin, one of the last lines of defense against life-threatening Gram-positive infections. Here, we report the crystal structure of Staphylococcus aureus DDl (StaDDl) and its cocrystal structures with 3-chloro-2,2-dimethyl-N-[4(trifluoromethyl)phenyl]propanamide (inhibitor 1) (Ki=4 microM against StaDDl) and with ADP, one of the reaction products, at resolutions of 2.0, 2.2, and 2.6 A, respectively. The overall structure of StaDDl can be divided into three distinct domains. The inhibitor binds to a hydrophobic pocket at the interface of the ...

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P2 MYELIN PROTEIN; D-ALANINE LIGASE; RELATE 2 SETS; 3-DIMENSIONAL STRUCTURE; DATA-BANK; RIBONUCLEOTIDE REDUCTASE; TRANSPORT PROTEINS; BINDING PROTEIN; ALIGNMENT; REFINEMENT ...

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Autore: ExtremeTech As the human race has advanced, weve made the process of creating products extremely efficient. Assembly line factories litter the planets

Crewe, 27 November 2015) The very first production Bentley Bentayga, the catalyst for one of the biggest investment programmes in the companys history, today left the assembly line at Bentleys iconic headquarters in Crewe, UK.. Four years on from the initial concept stage, during which time over 1,500 UK jobs have been created, the car - part of an £840 million investment programme - will now enter full production, with deliveries to customers starting in January 2016. Wolfgang Dürheimer, Chairman and Chief Executive of Bentley Motors, said: Bentley Bentayga will be the benchmark against which all other SUVs are measured, defining a new segment - the luxury SUV.. This car is a celebration of UK manufacturing at its very best, not only reinforcing our commitment to industry in this country, job creation and significant investment, but to our home in Crewe. This is an important moment in our history, where we reflect and celebrate, but also look ahead to delivering this extraordinary car to ...

For the past two decades, we have studied and engineered enzymatic assembly lines called polyketide synthases that catalyze the biosynthesis of structurally complex and medicinally fascinating antibiotics in bacteria. An example of such an assembly line is found in the erythromycin biosynthetic pathway. Our current focus is on understanding the structure and mechanism of this polyketide synthase. At the same time, we are developing methods to decode the vast and growing number of orphan polyketide assembly lines in the sequence databases ...

ABSTRACT Enzymes that cleave ATP to activate carboxylic acids play essential roles in primary and secondary metabolism in all domains of life. Class I

Precise Probing of Residue Roles by NRPS Code Swapping: Mutation, Enzymatic Characterization, Modeling, and Substrate Promiscuity of Aryl Acid Adenylation Domains

Human TTLL1 partial ORF ( NP_036395.1, 324 a.a. - 423 a.a.) recombinant protein with GST-tag at N-terminal. (H00025809-Q01) - Products - Abnova

Shop a large selection of Proteins A-Z products and learn more about Novus Biologicals TTLL7 Recombinant Protein Antigen Quantity: 100µg:Life Quantity: 100µg.

Peptide name products (sold by Zazzle ) featuring the name : LifeScience Click on the product descriptions or images to visit the Zazzle product page where you can buy the peptide name product.

NRPS/PKS substrate predictor uses a HMM-based approach to predict specificities of NRPS A-domains and PKS AT domains.. Reference:. ...

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A platform (walker) moves along a track, past several parts-handling devices, each of which can add a piece to the product - or not, depending on the programming of the system. This is a robotic, mechanical, digital, programmable system, built...

Third in our Open Boot series, Vanessa McCloskey opens the boot of the edition-driven project Assembly Line by artist Shane Bradford to see what rolls off their conveyor belt for...

The U.S. economy may still be slumping, but two analysts are predicting better times for manufacturing companies in the United States.

JAVA Column name name unique true private String name DDL name varchar 255 constraint uq customer name unique name which at least in MySQL is not a valid constraint name

This is a csh script that generates an imaging protocol file for use by the ITC18. This script is complicated and shouldnt be used as is. Camera trigger is assumed to be connect to TTL output 0. Shutters 1,2,3 are connected to TTL ouput 1,2,3. EPI and TIRF are switches that activate shutters 4,5 connected to TTL output 4 and 5. Filter positions are for a Sutter 10-2, using TTL outputs 8-15 found on the back of the ITC18. This script is for a very advanced user ...

We bid a fond farewell to what is arguably American Hondas least loved offering. looking to the sales numbers, what came off the assembly line in 2010 as the

I picked up one of these last year for less than £10, and in perfect working condition; the meter is exactly the same as that on my Nikon F100. Ive...

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