Catalyzes the condensation of ATP and 5-phosphoribose 1-diphosphate to form N-(5-phosphoribosyl)-ATP (PR-ATP). Has a crucial role in the pathway because the rate of histidine biosynthesis seems to be controlled primarily by regulation of HisG enzymatic activity (By similarity).
Abstract: Allosteric modulation of catalysis is a common regulatory strategy of flux-controlling biosynthetic enzymes. The enzyme ATP phosphoribosyltransferase (ATPPRT) catalyses the first reaction in histidine biosynthesis, the magnesium-dependent condensation of ATP and 5-phospho--D-ribosyl-1-pyrophosphate (PRPP) to generate N1-(5-phospho--D-ribosyl)-ATP (PRATP) and pyrophosphate (PPi). ATPPRT is allosterically inhibited by the final product of the pathway, histidine. Hetero-octameric ATPPRT consists of four catalytic subunits (HisGS) and four regulatory subunits (HisZ) engaged in intricate catalytic regulation. HisZ enhances HisGS catalysis in the absence of histidine while mediating allosteric inhibition in its presence. Here we report HisGS structures for the apoenzyme and complexes with substrates (PRPP, PRPP-ATP, PRPP-ADP), product (PRATP), and inhibitor (AMP), along with ATPPRT holoenzyme structures in complexes with substrates (PRPP, PRPP-ATP, PRPP-ADP) and product (PRATP). These ...
Analysis of the redundant first step in His biosynthesis catalyzed by ATP phosphoribosyl transferase required the construction of plants heterozygous for knockout alleles of both HISN1A (At1g58080) and HISN1B (At1g09795). The mutant alleles examined contained insertions near the beginning (hisn1b-1) or middle (hisn1a-1) of the coding region. Double knockouts for other redundant HISN genes could not be constructed because confirmed insertions remain to be identified for HISN5B and HISN6B. Twenty progeny plants from a selfed double heterozygote (AaBb) segregating for both hisn1a-1 (a) and hisn1b-1 (b) were PCR genotyped and screened for defects in seed and ovule development. The following plants were identified: AABb (5), AAbb (2), AaBB (5), and AaBb (8). Despite the small sample size, these results are consistent with two important conclusions supported by further studies: reduced transmission of double knockout gametes (ab) and embryo lethality of double homozygotes (aabb). No viable double ...
Ribbon representation of the structure of an enzyme known as ATP-PRT from TB bacteria (blue), bound to an allosteric activator (pink).
In polarized epithelial cells, vectorial protein trafficking is important for transporting specific membrane proteins to generate distinct apical and basolateral membrane protein compositions. The Exocyst is a conserved hetero-octameric protein complex, which regulates different aspects of protein trafficking, including tethering of the Golgi-derived vesicles to target membranes. Two of the Exocyst subunits, Sec5 and Exo84, competitively bind to the small GTPases, RalA and RalB, in a GTP-dependent manner. Although Ral GTPases have been proposed to mediate assembly of Exocyst holocomplexes, we hypothesize that they actually serve to allosterically regulate Exocyst functions by promoting association or disassociation of additional factors. Previous studies have shown that active RalA, but not RalB, accelerated basolateral exocytosis of E-cadherin. In contrast, knockdown of RalB, but not RalA, disrupts endocytosis of E-cadherin. However, mechanisms by which association of Ral GTPases with Sec5 and Exo84
Metabolism. Shui, Wang [1], Guirong, Zhang [2], Wang, Hongyun [3], Ulanov, Alexander [3], Lozovaya, Vera [3], Lin, Yun [4]. A regulatory role of histidine in Arabidopsis metabolism and growth revealed by the low oil 1 mutant that corresponds to ATP-Phosphoribosyl Transferase 1, a key enzyme of histidine biosynthesis.. Amino acid sensory mechanisms are known to coordinate metabolism and growth in microbes and animals. However, evidence for their existence in plants has been elusive. In a genetic screen for Arabidopsis seed oil and protein deposition mutants, the low oil 1 (loo1) was isolated and map-based gene cloning identified a missense mutation in the first histidine biosynthetic enzyme ATP-phosphoribosyl transferase 1 (ATP-PRT1). The loo1 mutant exhibited development and growth defects throughout the entire lifespan. The severely retarded root elongation of loo1 seedlings was rescued by supplemental histidine in the growth medium. Transcript and metabolite profiling and real-time RT-PCR ...
TY - JOUR. T1 - Identification of novel bacterial histidine biosynthesis inhibitors using docking, ensemble rescoring, and whole-cell assays. AU - Henriksen,Signe Teuber. AU - Liu,J.. AU - Estiu,G.. AU - Oltvai,Z.N.. AU - Wiest,O.. PY - 2010. Y1 - 2010. N2 - The rapid spread on multidrug-resistant strains of Staphylococcus aureus requires not just novel treatment options, but the development of faster methods for the identification of new hits for drug development. The exponentially increasing speed of computational methods makes a more extensive use in the early stages of drug discovery attractive if sufficient accuracy can be achieved. Computational target identification using systems-level methods suggested the histidine biosynthesis pathway as an attractive target against S. aureus. Potential inhibitors for the pathway were identified through docking, followed by ensemble rescoring, that is sufficiently accurate to justify immediate testing of the identified compounds by whole-cell assays, ...
The Genetics Society of America (GSA), founded in 1931, is the professional membership organization for scientific researchers and educators in the field of genetics. Our members work to advance knowledge in the basic mechanisms of inheritance, from the molecular to the population level.. Online ISSN: 1943-2631. ...
Imidazoleglycerol-phosphate dehydratase, catalyzes the sixth step in histidine biosynthesis; mutations cause histidine auxotrophy and sensitivity to Cu, Co, and Ni salts; transcription is regulated by general amino acid control via ...
Displaying operon conservation. Part A shows that the order of genes belonging to the histidine operon is well conserved in this set of proteobacterial genomes.
Isolate DNA from soil. NucleoSpin Soil DNA purification kit removes humic acid & PCR inhibitors from soil samples. Superior performance & great value.
This clade of sequences is highly similar to the HisF protein, but generally represents the second HisF homolog in the genome where the other is an authentic HisF observed in the context of a complete histidine biosynthesis operon. The similarity between these WbuZ sequences and true HisFs is such that often the closest match by BLAST of a WbuZ is a HisF. Only by making a multiple sequence alignment is the homology relationship among the WbuZ sequences made apparent. WbuZ genes are invariably observed in the presence of a homolog of the HisH protein (designated WbuY) and a proposed N-acetyl sugar amidotransferase designated in WbuX in E. coli [1], IfnA in P. aeriginosa [2] and PseA in C. jejuni [3]. Similarly, this trio of genes is invariably found in the context of saccharide biosynthesis loci. It has been shown that the WbuYZ homologs are not essential components of the activity expressed by WbuX, leading to the proposal that these to proteins provide ammonium ions to the amidotransferase when ...
The Genetics Society of America (GSA), founded in 1931, is the professional membership organization for scientific researchers and educators in the field of genetics. Our members work to advance knowledge in the basic mechanisms of inheritance, from the molecular to the population level.. Online ISSN: 1943-2631. ...
Hello, This question might seem easy, but I found it not so obvious as I thought about it more: What does rate limiting mean to you ? It is used quite often, and not only in biology. The example I am dealing with is a common one, a metabolic pathway. The simplest way to see it, is that there is not RenoughS of the first enzyme on the pathway and RplentyS of the following enzymes. When more of the first enzyme is made, the flux through the pathway increases in a direct (not necessarily linear) function of this first enzyme. Does it mean that this first enzyme is used at saturation of its substrate(s) ? If not, the element that keeps those substrate(s) constant would be the real rate limiting step by providing the right flux of substrate so as to keep it constant ! If that flux does not change, an increase in the quantity and consequently in flux of the first enzyme would have the effect of lowering the concentration of its substrate until the activity was restored to its original value ! I feel ...
Steroidal glycoalkaloids (SGAs) are plant secondary metabolites known to be toxic to animals and humans and that have putative roles in defense against pests. The proposed mechanisms of SGA toxicity are sterol-mediated disruption of membranes and inhibition of cholinesterase activity in neurons. It has been suggested that phytopathogenic microorganisms can overcome SGA toxicity by enzymatic deglycosylation of SGAs. Here, we have explored SGA-mediated toxicity toward the invasive oomycete Phytophthora infestans, the causative agent of the late blight disease in potato and tomato, as well as the potential for SGA deglycosylation by this species. Our growth studies indicate that solanidine, the nonglycosylated precursor of the potato SGAs a-chaconine and a-solanine, has a greater physiological impact than its glycosylated forms. All of these compounds were incorporated into the mycelium, but only solanidine could strongly inhibit the growth of P. infestans in liquid culture. Genes encoding several ...
Contrasting effects of nicotianamine synthase knockdown on zinc and nickel tolerance and accumulation in the zinc/cadmium hyperaccumulator Arabidopsis halleri ...
Histidine biosynthesis bifunctional protein HisIE; Protein involved in phosphoribosyl-AMP cyclohydrolase activity, phosphoribosyl-ATP diphosphatase activity and histidine biosynthetic process; In the N-terminal section; belongs to the PRA-CH family (213 aa ...
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