Vacuolar Proton-Translocating ATPases
Proton Pump Inhibitors
Magnetic Resonance Spectroscopy
Plasma Membrane Calcium-Transporting ATPases
Molecular Sequence Data
Amino Acid Sequence
Cation Transport Proteins
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Protein Structure, Tertiary
Electron Transport Complex IV
Bacterial Proton-Translocating ATPases
Biological Transport, Active
Chloroplast Proton-Translocating ATPases
Sequence Homology, Amino Acid
Saccharomyces cerevisiae Proteins
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
Gram-Negative Chemolithotrophic Bacteria
Protein Structure, Secondary
Protein Structure, Quaternary
Membrane Transport Proteins
Menkes Kinky Hair Syndrome
Proteasome Endopeptidase Complex
Phospholipid Transfer Proteins
Nuclear Magnetic Resonance, Biomolecular
Amino Acid Substitution
Amino Acid Motifs
Histamine H2 Antagonists
Electrophoresis, Polyacrylamide Gel
Molecular Motor Proteins
Pemphigus, Benign Familial
Radiotherapy Planning, Computer-Assisted
ATP-Binding Cassette Transporters
Carbonic Anhydrase II
Mutation of the mitochrondrially encoded ATPase 6 gene modeled in the ATP synthase of Escherichia coli. (1/110)Defects of respiratory chain protein complexes and the ATP synthase are becoming increasingly implicated in human disease. Recently, mutations in the ATPase 6 gene have been shown to cause several different neurological disorders. The product of this gene is homologous to the a subunit of the ATP synthase of Escherichia coli. Here, mutations equivalent to those described in humans have been introduced into the a subunit of E. coli by site-directed mutagenesis, and the effects of these mutations on the ATPase activity, ATP synthesis and ability of the enzyme to pump protons studied in detail. The effects of the mutations varied considerably. The mutation L262P (9185 T-C equivalent) caused a 70% loss of ATP synthesis activity, reduced DCCD sensitivity, and lowered proton pumping activity. The L207P (8993 T-C equivalent) reduced ATP synthesis by 50%, affected DCCD sensitivity, while proton pumping was only marginally affected when measured by the standard AMCA quenching assay. The other mutations studied affected the functioning of the ATP synthase much less. The results confirm that modeling of these point mutations in the E. coli enzyme is a useful approach to determining how alterations in the ATPase 6 gene affect enzyme function and, therefore, how a pathogenic effect can be exerted. (+info)
Redox regulation of the rotation of F(1)-ATP synthase. (2/110)In F(1)-ATPase, the smallest known motor enzyme, unidirectional rotation of the central axis subunit gamma is coupled to ATP hydrolysis. In the present study, we report the redox switching of the rotation of this enzyme. For this purpose, the switch region from the gamma subunit of the redox-sensitive chloroplast F(1)-ATPase was introduced into the bacterial F(1)-ATPase. The ATPase activity of the obtained complex was increased up to 3-fold upon reduction (Bald, D., Noji, H., Stumpp, M. T., Yoshida, M. & Hisabori, T. (2000) J. Biol. Chem. 275, 12757-12762). Here, we successfully observed the modulation of rotation of gamma in this chimeric complex by changes in the redox conditions. In addition we revealed that the suppressed enzymatic activity of the oxidized F(1)-ATPase complex was characterized by more frequent long pauses in the rotation of the gamma subunit. These findings obtained by the single molecule analysis therefore provide new insights into the mechanisms of enzyme regulation. (+info)
Functions and ATP-binding responses of the twelve histidine residues in the TF1-ATPase beta subunit. (3/110)The C2 proton signals of all (twelve) histidine residues of the TF1 beta subunit in the 1H-NMR spectrum have been identified and assigned by means of pH change experiments and site-directed substitution of histidines by glutamines. pH and ligand titration experiments were carried out for these signals. Furthermore, the ATPase activity of the reconstituted alpha3beta3gamma complex was examined for the twelve mutant beta subunits. Two of three conserved histidines, namely, His-119 and 324, were found to be important for expression of the ATPase activity. The former fixes the N-terminal domain to the central domain. His-324 is involved in the formation of the interface essential for the alpha3beta3gamma complex assembly. The other conserved residue, His-363, showed a very low pK(a), suggesting that it is involved in the tertiary structure formation. On the binding of a nucleotide, only the signals of His-173, 179, 200, and 324 shifted. These histidines are located in the hinge region, and its proximity, of the beta subunit. This observation provided further support for the conformational change of the beta monomer from the open to the closed form on the binding of a nucleotide proposed by us [Yagi et al. (1999) Biophys. J. 77, 2175-2183]. This conformational change should be one of the essential driving forces in the rotation of the alpha3beta3gamma complex. (+info)
Genetic diversity of Pasteurella multocida fowl cholera isolates as demonstrated by ribotyping and 16S rRNA and partial atpD sequence comparisons. (4/110)The genetic diversity of Pasteurella multocida, the aetiological agent of fowl cholera, was investigated. The strain collection comprised 69 clinical isolates representing a wide spectrum of hosts and geographic origin. The three type strains for the subspecies of P. multocida were also included. Avian isolates of P. multocida subsp. multocida and P. multocida subsp. septica did not represent separate lines by HpaII ribotyping and the two type strains of mammalian origin (porcine and cat bite) seemed to be representative of avian strains of P. multocida subspp. multocida and septica. By ribotyping, all P. multocida subsp. gallicida strains, except one chicken isolate and the type strain, clustered together. This indicated that the bovine type strain was not representative of this subspecies and that most strains of P. multocida subsp. gallicida are genetically related and may be distantly related to other P. multocida isolates, including those of avian origin. By 16S rRNA and atpD sequence comparisons of selected strains, including both P. multocida isolated from birds and mammals and selected distantly related Pasteurella species associated with birds and mammals, it was found that P. multocida is monophyletic. Extended DNA-DNA hybridizations are highly indicated since strains may exist which would connect the existing subspecies at species level. The considerable genetic diversity of P. multocida fowl cholera isolates is probably related to the clonal nature of this organism, resulting in many divergent lines. (+info)
Phylogenies of atpD and recA support the small subunit rRNA-based classification of rhizobia. (5/110)The current classification of the rhizobia (root-nodule symbionts) assigns them to six genera. It is strongly influenced by the small subunit (16S, SSU) rRNA molecular phylogeny, but such single-gene phylogenies may not reflect the evolution of the genome as a whole. To test this, parts of the atpD and recA genes have been sequenced for 25 type strains within the alpha-Proteobacteria, representing species in Rhizobium, Sinorhizobium, Mesorhizobium, Bradyrhizobium, Azorhizobium, Agrobacterium, Phyllobacterium, Mycoplana and Brevundimonas. The current genera Sinorhizobium and Mesorhizobium are well supported by these genes, each forming a distinct phylogenetic clade with unequivocal bootstrap support. There is good support for a Rhizobium clade that includes Agrobacterium tumefaciens, and the very close relationship between Agrobacterium rhizogenes and Rhizobium tropici is confirmed. There is evidence for recombination within the genera Mesorhizobium and Sinorhizobium, but the congruence of the phylogenies at higher levels indicates that the genera are genetically isolated. rRNA provides a reliable distinction between genera, but genetic relationships within a genus may be disturbed by recombination. (+info)
Coupling of proton flow to ATP synthesis in Rhodobacter capsulatus: F(0)F(1)-ATP synthase is absent from about half of chromatophores. (6/110)F(0)F(1)-ATP synthase (H(+)-ATP synthase, F(0)F(1)) utilizes the transmembrane protonmotive force to catalyze the formation of ATP from ADP and inorganic phosphate (P(i)). Structurally the enzyme consists of a membrane-embedded proton-translocating F(0) portion and a protruding hydrophilic F(1) part that catalyzes the synthesis of ATP. In photosynthetic purple bacteria a single turnover of the photosynthetic reaction centers (driven by a short saturating flash of light) generates protonmotive force that is sufficiently large to drive ATP synthesis. Using isolated chromatophore vesicles of Rhodobacter capsulatus, we monitored the flash induced ATP synthesis (by chemoluminescence of luciferin/luciferase) in parallel to the transmembrane charge transfer through F(0)F(1) (by following the decay of electrochromic bandshifts of intrinsic carotenoids). With the help of specific inhibitors of F(1) (efrapeptin) and of F(0) (venturicidin), we decomposed the kinetics of the total proton flow through F(0)F(1) into (i) those coupled to the ATP synthesis and (ii) the de-coupled proton escape through F(0). Taking the coupled proton flow, we calculated the H(+)/ATP ratio; it was found to be 3.3+/-0.6 at a large driving force (after one saturating flash of light) but to increase up to 5.1+/-0.9 at a smaller driving force (after a half-saturating flash). From the results obtained, we conclude that our routine chromatophore preparations contained three subsets of chromatophore vesicles. Chromatophores with coupled F(0)F(1) dominated in fresh material. Freezing/thawing or pre-illumination in the absence of ADP and P(i) led to an increase in the fraction of chromatophores with at least one de-coupled F(0)(F(1)). The disclosed fraction of chromatophores that lacked proton-conducting F(0)(F(1)) (approx. 40% of the total amount) remained constant upon these treatments. (+info)
The topology of the proton translocating F0 component of the ATP synthase from E. coli K12: studies with proteases. (7/110)The accessibility of the three F0 subunits a, b and c from the Escherichia coli K12 ATP synthase to various proteases was studied in F1-depleted inverted membrane vesicles. Subunit b was very sensitive to all applied proteases. Chymotrypsin produced a defined fragment of mol. wt. 15,000 which remained tightly bound to the membrane. The cleavage site was located at the C-terminal region of subunit b. Larger amounts of proteases were necessary to attack subunit a (mol. wt. 30,000). There was no detectable cleavage of subunit c. It is suggested that the major hydrophilic part of subunit b extends from the membrane into the cytoplasm and is in contact with the F1 sector. The F1 sector was found to afford some protection against proteolysis of the b subunit in vitro and in vivo. Protease digestion had no influence on the electro-impelled H+ conduction via F0 but ATP-dependent H+ translocation could not be reconstituted upon binding of F1. A possible role for subunit b as a linker between catalytic events on the F1 component and the proton pathway across the membrane is discussed. (+info)
Membrane integration and function of the three F0 subunits of the ATP synthase of Escherichia coli K12. (8/110)Integration into the cytoplasmic membrane and function of the three F0 subunits, a, b and c, of the membrane-bound ATP synthase of Escherichia coli K12 were analysed in situations where synthesis of only one or two types of subunits was possible. This was achieved by combined use of atp mutations and plasmids carrying and expressing one or two of the atp genes coding for ATP synthase subunits. AU three F0 subunits were found to be required for the establishment of efficient H+ conduction. Subunits a and b individually as well as together were found to bind F1 ATPase to the membrane while subunit c did not. The ATPase activity bound to either of these single subunits, or in pairwise combinations, was not inhibited by N,N'-dicyclohexylcarbodiimide. Also ATP-dependent H+ translocation was not catalysed unless all three F0 subunits were present in the membrane. The integration into the membrane of the subunits a and b was independent of the presence of other ATP synthase subunits. (+info)
The hepatolenticular tract is a complex system of nerve fibers that connect the liver and other organs in the body, allowing for the exchange of information and coordination of bodily functions. HLD occurs when these nerve fibers are damaged or destroyed, leading to problems with brain function and communication.
The symptoms of HLD can vary depending on the severity of the damage and the specific areas of the brain affected. Common symptoms include difficulty with memory and cognitive function, poor coordination and balance, and changes in behavior and personality. In severe cases, HLD can lead to coma or even death.
There is currently no cure for HLD, but there are several treatments available that can help manage the symptoms and slow the progression of the disease. These may include medications to reduce inflammation and oxidative stress, as well as physical therapy and rehabilitation to improve cognitive and motor function. In some cases, liver transplantation may be necessary to treat underlying liver disease.
Overall, hepatobilayer degeneration is a serious condition that can have significant effects on brain function and quality of life. If you suspect that you or someone you know may be experiencing symptoms of HLD, it is important to seek medical attention as soon as possible to receive an accurate diagnosis and appropriate treatment.
The main symptoms of Menkes syndrome are:
1. Steel-gray or kinky hair, which starts to appear within the first few months of life.
2. Failure to thrive, poor muscle tone, and low birth weight.
3. Developmental delays and intellectual disability.
4. Seizures and poor coordination.
5. Poor immune function and recurrent infections.
6. Gradual loss of vision and hearing.
7. Osteoporosis and fragile bones.
8. Increased risk of liver disease, including cirrhosis and portal hypertension.
The diagnosis of Menkes syndrome is based on a combination of clinical findings, laboratory tests, and genetic analysis. Treatment is focused on managing the symptoms and preventing complications, and may include copper supplements, anticonvulsants, and other medications.
The prognosis for Menkes syndrome is poor, with most individuals dying in childhood or adolescence due to complications such as liver disease, infections, or seizures. However, some individuals may live into their 20s or 30s with appropriate management and care.
The symptoms of BFP typically appear in early adulthood and can include:
* Blisters and sores on the skin and mucous membranes
* Pain and discomfort
* Scarring and disfigurement
* Difficulty swallowing (in severe cases)
BFP is diagnosed through a combination of clinical evaluation, family history, and genetic testing. Treatment for the condition typically involves managing the symptoms and preventing complications. This may include:
* Topical medications to reduce inflammation and promote healing
* Oral medications to suppress the immune system and prevent further blistering
* Physical therapy to improve mobility and reduce pain
While there is no cure for BFP, early diagnosis and appropriate treatment can help to manage the symptoms and improve quality of life. The condition is typically inherited in an autosomal dominant pattern, which means that a single copy of the mutated gene is enough to cause the condition. However, some cases may be caused by spontaneous mutations rather than inheritance.
GER can be caused by a variety of factors, including:
* Weakening of the lower esophageal sphincter (LES), which allows stomach acid to flow back up into the esophagus.
* Delayed gastric emptying, which can cause food and stomach acid to remain in the stomach for longer periods of time and increase the risk of reflux.
* Obesity, which can put pressure on the stomach and cause the LES to weaken.
Symptoms of GER can include:
* Heartburn: a burning sensation in the chest that can radiate to the throat and neck.
* Regurgitation: the sensation of food coming back up into the mouth.
* Difficulty swallowing.
* Chest pain or tightness.
* Hoarseness or laryngitis.
If left untreated, GER can lead to complications such as esophagitis (inflammation of the esophagus), strictures (narrowing of the esophagus), and barrett's esophagus (precancerous changes in the esophageal lining).
Treatment options for GER include:
* Lifestyle modifications, such as losing weight, avoiding trigger foods, and elevating the head of the bed.
* Medications, such as antacids, H2 blockers, and proton pump inhibitors, to reduce acid production and relax the LES.
* Surgical procedures, such as fundoplication (a procedure that strengthens the LES) and laparoscopic adjustable gastric banding (a procedure that reduces the size of the stomach).
It is important to seek medical attention if symptoms persist or worsen over time, as GER can have serious complications if left untreated.