Structural and dynamic studies of Mycobacterium tuberculosis Adenylate kinase and it’s double mutant (A11S/E112K), using the NMR spectroscopy and Molecular dynamic simulation
DC Field | Value | Language |
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dc.contributor.author | 원호식 | - |
dc.date.accessioned | 2021-06-23T00:29:49Z | - |
dc.date.available | 2021-06-23T00:29:49Z | - |
dc.date.issued | 2009-10-25 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/24342 | - |
dc.description.abstract | Adenylate kinase from Mycobacterium tuberculosis (AKmt), a protein of 181 residues is short variant with low similarity with the eukaryote cytosolic AKs. It is an essential enzyme for bacterial survival and it.s catalytic activity is lower than other AKs((AKe, AK1 etc). But recently we found that catalytic activity of two point double mutant(A11S, E122K) of AKmt, AKmtDM was 12 fold increased. In this work, a solution-state NMR approach and Molecular Dynamics simulation were used to probe the structural and dynamic distinction of AKmt and AKmtDM. Firstly, chemical shift analysis of AKmtDM, using the 1H-15N HSQC experiment, show that ATP binding P-loop(7-13) and LID domain and include LID domain surrounding residues(115~135), are slightly perturbed(δw.0.1~03ppm). It suggests that AKmtDM backbone structure is differ from AKmt at ATP binding active site and it’s structural perturbation maybe induce significant backbone rearrangement and eventually produce the difference of catalytic activity. To closely understand structural and dynamic motion, we perform 10ns MD computer simulation using the explicit water system. Principal component analysis of MD simulation, performed on AKmt and AKmtDM, shows that the sums of the eigenvalues, related to the overall fluctuations, are 4.85nm2 for AKmtDM and 1.3 fold larger than that of AKmt. Moreover, simulation in AKmtDM reveals that the first 3 mode account for 70% of the total fluctuation. The main contribution to the overall enzyme fluctuation is given by the LID, AMP-binding domain and P-loop (AKmt is LID, AMP-binding domain motion only) and especially fluctuations of LID and P-loop in AKmtDM contribute critical conformational transition. MD simulation also show that stable salt bridge K122-E118 at the LID domain interface and hydrogen bonding K122-S11 LID-Core interaction stabilize the open conformation. These results provide specific knowledge about structural dynamic motion of AKmt/AKmtDM and more generally suggest that molecular dynamics simulation can provide valuable information for identifying catalytic activity | - |
dc.title | Structural and dynamic studies of Mycobacterium tuberculosis Adenylate kinase and it’s double mutant (A11S/E112K), using the NMR spectroscopy and Molecular dynamic simulation | - |
dc.type | Conference | - |
dc.citation.conferenceName | The 3rd Asia pacific NMR | - |
dc.citation.conferencePlace | Jeju, Korea | - |
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