Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent advances in functional genomics have helped generate large-scale high-throughput protein interaction data. Such networks, though extremely valuable towards molecular level understanding of cells, do not provide any direct information about the regions (domains) in the proteins that mediate the interaction. Here, we performed co-evolutionary analysis of domains in interacting proteins in order to understand the degree of co-evolution of interacting and non-interacting domains. Using a combination of sequence and structural analysis, we analyzed protein-protein interactions in F1-ATPase, Sec23p/Sec24p, DNA-directed RNA polymerase and nuclear pore complexes, and found that interacting domain pair(s) for a given interaction exhibits higher level of co-evolution than the non-interacting domain pairs. Motivated by this finding, we developed a computational method to test the generality of the observed trend, and to predict large-scale domain-domain interactions. Given a protein-protein interaction, the proposed method predicts the domain pair(s) that is most likely to mediate the protein interaction. We applied this method on the yeast interactome to predict domain-domain interactions, and used known domain-domain interactions found in PDB crystal structures to validate our predictions. Our results show that the prediction accuracy of the proposed method is statistically significant. Comparison of our prediction results with those from two other methods reveals that only a fraction of predictions are shared by all the three methods, indicating that the proposed method can detect known interactions missed by other methods. We believe that the proposed method can be used with other methods to help identify previously unrecognized domain-domain interactions on a genome scale, and could potentially help reduce the search space for identifying interaction sites.
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PMID:Co-evolutionary analysis of domains in interacting proteins reveals insights into domain-domain interactions mediating protein-protein interactions. 1694 97

Scrub typhus, caused by infection with Orientia tsutsugamushi, is probably the most common severe rickettsial disease. Early diagnosis followed by treatment with antibiotics such as doxycycline or chloramphenicol usually quickly decreases fever in patients, and they often recover well from other symptoms of the disease. However, poorly responsive cases have been reported from northern Thailand and southern India. In order to identify protein factors that may be partially responsible for differential drug sensitivity of isolates of Orientia, we compared the protein profiles of doxycycline sensitive (Karp) versus (vs.) insensitive (AFSC4 and AFSC7) isolates. Tryptic peptides from both total water-soluble proteins and from protein spots separated by 2D-PAGE were analyzed using LC-MS/MS. The identity of each protein was established using the published genomic sequence of Boryong strain O. tsutsugamushi. The profiles of protein released into water from these isolates were quite different. There were 10 proteins detected only in AFSC4, 3 only in Karp, and 1 only in AFSC7. Additionally, there were 2 proteins not detected only in AFSC4, 4 not found only in Karp, and 3 not found only in AFSC-7. A comparison of 2D-PAGE protein profiles of drug sensitive strain versus (vs.) insensitive isolates has led to the identification of 14 differentially expressed or localized proteins, including elongation factor Ts and Tu, DNA-directed RNA polymerase alpha-subunit, ATP synthase beta-subunit, and several hypothetical proteins. These data confirm the tremendous proteomic diversity of isolates of Orientia and suggest that drug insensitivity in this species may arise from multiple mechanisms.
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PMID:Comparative proteomic analysis of antibiotic-sensitive and insensitive isolates of Orientia tsutsugamushi. 1953 61

This work reports on the metabolic response in the induction of the viable but nonculturable (VBNC) state of the seafood enteropathogen Vibrio parahaemolyticus, as determined by analyzing the corresponding change in protein profiles. V. parahaemolyticus ST550 was incubated at 4 degrees C in the Morita mineral salt-0.5% NaCl medium to induce the VBNC state in six weeks. Starving the cells by incubation at 25 degrees C for 24 h prior to 4 degrees C incubation inhibited the cells from entering VBNC state. Protein profiles were determined by two-dimensional polyacrylamide gel electrophoresis and the proteins which were enhanced in the VBNC induction/VBNC state or strongly down-regulated in the starved cells were identified by mass spectrophotometry. The 13 up-regulated proteins are known to be associated with transcription (two homologues of alpha subunit DNA-directed RNA polymerase, phosphoribosylaminoimidazole carboxamide formyltransferase/IMP cyclohydrolase), translation (ribosomal protein S1, two homologues of elongation factor TU, elongation factor EF-G), ATP synthase (F1 alpha subunit), gluconeogenesis-related metabolism (dihydrolipoamide acetyltransferase, glyceraldehyde 3-phosphate dehydrogenase), antioxidants (2 homologues of peroxiredoxins, AhpC/Tsa family) and a conserved hypothetical protein with unknown function. Expressions of the genes encoding four of these proteins were at high levels in the second week of VBNC induction; declined afterwards, and were down-regulated in the starved cells. These proteins may play important roles in the induction or maintenance of VBNC V. parahaemolyticus. The results of this investigation improve our understanding of the metabolic activities in the VBNC state of bacteria.
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PMID:Change of protein profiles in the induction of the viable but nonculturable state of Vibrio parahaemolyticus. 1973 55