Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using purified recombinant human ventricular myosin light chain 1 (HVMLC1) as the antigen, three monoclonal antibodies, designated C8, C9 and B12, were prepared. Immunoblot experiments demonstrated that all monoclonal antibodies could react with the ventricular myosin light chain 1 isolated from different sources, such as human, rat or pig. It was also demonstrated that C8 was directed against the NN part of the N-fragment (amino acid 1-40) of HVMLC1, and both C9 and B12 against the C-fragment (amino acid 99-195). The affinity constants of C8, C9 and B12 were 3.20 x 10(8), 8.600 x 10(7) and 1.770 x 10(8) M(-1), respectively, determined by non-competitive ELISA. The isotype of B12 was determined as IgG2a, whereas the isotype of both C8 and C9 were IgG1. In the presence of C9 or B12, the actin-activated Mg(2+)ATPase activity of myosin was greatly inhibited, but there was almost no effect on the Mg(2+) ATPase activity for C8. B12 and C9 also inhibited the superprecipitation of porcine cardiac native actomyosin (myosin B) and reconstituted actomyosin, but C8 did not. The results indicate that all three monoclonal antibodies could bind the intact myosin molecule, but B12 and C9 might more easily react with epitopes located in the C-fragment of HVMLC1. The inhibitory effects of B12 and C9 on ATPase activity and superprecipitation assays show that light chain 1, particularly the C-fragment domain, is involved in the modulation of the actin-activated Mg(2+) ATPase activity of myosin and, as a consequence, plays an essential role in the interaction of actin and myosin.
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PMID:Preparation of monoclonal antibodies against human ventricular myosin light chain 1 (HVMLC1) for functional studies. 1695 1

Inherited disorders of vitamin B12 (cobalamin) have provided important clues to how this vitamin, which is essential for hematological and neurological function, is transported and metabolized. We describe a new disease that results in failure to release vitamin B12 from lysosomes, which mimics the cblF defect caused by LMBRD1 mutations. Using microcell-mediated chromosome transfer and exome sequencing, we identified causal mutations in ABCD4, a gene that codes for an ABC transporter, which was previously thought to have peroxisomal localization and function. Our results show that ABCD4 colocalizes with the lysosomal proteins LAMP1 and LMBD1, the latter of which is deficient in the cblF defect. Furthermore, we show that mutations altering the putative ATPase domain of ABCD4 affect its function, suggesting that the ATPase activity of ABCD4 may be involved in intracellular processing of vitamin B12.
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PMID:Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism. 2292 74

In all kingdoms of life, ATP binding cassette (ABC) transporters are essential to many cellular functions. In this large superfamily of proteins, two catalytic sites hydrolyze ATP to power uphill substrate translocation. A central question in the field concerns the relationship between the two ATPase catalytic sites: Are the sites independent of one another? Are both needed for function? Do they function cooperatively? These issues have been resolved for type I ABC transporters but never for a type II ABC transporter. The many mechanistic differences between type I and type II ABC transporters raise the question whether in respect to ATP hydrolysis the two subtypes are similar or different. We have addressed this question by studying the Escherichia coli vitamin B12 type II ABC transporter BtuCD. We have constructed and purified a series of BtuCD variants where both, one, or none of the ATPase sites were rendered inactive by mutation. We find that, in a membrane environment, the ATPase sites of BtuCD are highly cooperative with a Hill coefficient of 2. We also find that, when one of the ATPase sites is inactive, ATP hydrolysis and vitamin B12 transport by BtuCD is reduced by 95%. These exact features are also shared by the archetypical type I maltose ABC transporter. Remarkably, mutants that have lost 95% of their ATPase and transport capabilities still retain the ability to fully use vitamin B12 in vivo. The results demonstrate that, despite the many differences between type I and type II ABC transporters, the fundamental mechanism of ATP hydrolysis remains conserved.
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PMID:A single intact ATPase site of the ABC transporter BtuCD drives 5% transport activity yet supports full in vivo vitamin B12 utilization. 2351 27

Autoimmune gastritis is a silent and highly prevalent disease that only becomes clinically manifested with progression to corpus atrophy and development of iron deficient or B12-deficient (pernicious) anaemia. Autoimmune gastritis is associated with autoimmune thyroiditis and type 1 diabetes mellitus. Corpus atrophy may be complicated by gastric carcinoids and gastric cancer. Laboratory diagnosis of autoimmune gastritis rests on serum biomarkers of antibody to parietal cell H/K ATPase and intrinsic factor and corpus atrophy on serum biomarkers of gastrin and pepsinogen levels. Subjects with asymptomatic parietal cell antibody should be regularly assessed for serum biomarkers for progression to corpus atrophy, development of iron and B12 deficiency anaemia and for associated autoimmune thyroiditis and type 1 diabetes mellitus.
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PMID:Diagnosis and classification of autoimmune gastritis. 2442 93

Thermodynamically unfavourable electron transfers are enabled by coupling to an energy-supplying reaction. How the energy is transduced from the exergonic to the endergonic process is largely unknown. Here we provide the structural basis for an energy transduction process in the reductive activation of B12-dependent methyltransferases. The transfer of one electron from an activating enzyme to the cobalamin cofactor is energetically uphill and relies on coupling to an ATPase reaction. Our results demonstrate that the key to coupling is, besides the oxidation state-dependent complex formation, the conformational gating of the electron transfer. Complex formation induces a substitution of the ligand at the electron-accepting Co ion. Addition of ATP initiates electron transfer by provoking conformational changes that destabilize the complex. We show how remodelling of the electron-accepting Co(2+) promotes ATP-dependent electron transfer; an efficient strategy not seen in other electron-transferring ATPases.
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PMID:ATP-induced electron transfer by redox-selective partner recognition. 2510 7

The current study aimed to identify the differences presented in the proteome of fluconazole-susceptible isolates of Candida glabrata compared to those with fluconazole-resistant ones. Two-dimensional differential gel electrophoresis was applied to identify proteins that were differentially expressed in fluconazole-susceptible and fluconazole-resistant isolates of C. glabrata. Eight proteins including aspartyl-tRNA synthetase, translation elongation factor 3, 3-phosphoglycerate kinase, ribosomal protein L5, coproporphyrinogen III oxidase, pyruvate kinase, G-beta like protein, and F1F0-ATPase alpha subunit were found to be more abundantly represented, while four proteins including vitamin B12-(cobalamin)-independent isozyme of methionine synthase, microtubule-associated protein, adenylosuccinate synthetase, and aldose reductase were found to be less abundantly represented in fluconazole-resistant strains versus those with fluconazole-susceptible ones. These differentially expressed proteins were primarily associated with energy metabolism, stress response, and macromolecule synthesis. Proteins associated with energy metabolism, stress response, and macromolecule synthesis may play a role in the development of fluconazole resistance in the clinical isolates of C. glabrata. Multiple different mechanisms are involved in the development of fluconazole resistance in C. glabrata. These findings provide a scientific basis for discovering new genes and mechanisms associated with fluconazole resistance in C. glabrata.
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PMID:Differentially expressed proteins in fluconazole-susceptible and fluconazole-resistant isolates of Candida glabrata. 2619 41

Proton pump inhibitors (PPIs) are known as a class of pharmaceutical agents that target H+/K+-ATPase, which is located in gastric parietal cells. PPIs are widely used in the treatment of gastric acid-related diseases including peptic ulcer disease, erosive esophagitis and gastroesophageal reflux disease, and so on. These drugs present an excellent safety profile and have become one of the most commonly prescribed drugs in primary and specialty care. Except for gastric acid-related diseases, PPIs can also be used in the treatment of Helicobacter pylori infection, viral infections, respiratory system diseases, cancer and so on. Although PPIs are mainly used short term in patients with peptic ulcer disease, nowadays these drugs are increasingly used long term, and frequently for a lifetime, for instance in patients with typical or atypical symptoms of gastroesophageal reflux disease and in NSAID or aspirin users at risk of gastrotoxicity and related complications including hemorrhage, perforation and gastric outlet obstruction. Long-term use of PPIs may lead to potential adverse effects, such as osteoporotic fracture, renal damage, infection (pneumonia and clostridium difficile infection), rhabdomyolysis, nutritional deficiencies (vitamin B12, magnesium and iron), anemia and thrombocytopenia. In this article, we will review some novel uses of PPIs in other fields and summarize the underlying adverse reactions.
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PMID:A Review of the Novel Application and Potential Adverse Effects of Proton Pump Inhibitors. 2842 47


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