3tmk
From Proteopedia
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'''CRYSTAL STRUCTURE OF YEAST THYMIDYLATE KINASE COMPLEXED WITH THE BISUBSTRATE INHIBITOR TP5A AT 2.0 A RESOLUTION: IMPLICATIONS FOR CATALYSIS AND AZT ACTIVATION''' | '''CRYSTAL STRUCTURE OF YEAST THYMIDYLATE KINASE COMPLEXED WITH THE BISUBSTRATE INHIBITOR TP5A AT 2.0 A RESOLUTION: IMPLICATIONS FOR CATALYSIS AND AZT ACTIVATION''' | ||
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[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: | + | [[Category: DTMP kinase]] |
[[Category: Brundiers, R.]] | [[Category: Brundiers, R.]] | ||
[[Category: Goody, R S.]] | [[Category: Goody, R S.]] | ||
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[[Category: Reinstein, J.]] | [[Category: Reinstein, J.]] | ||
[[Category: Schlichting, I.]] | [[Category: Schlichting, I.]] | ||
| - | [[Category: | + | [[Category: Kinase]] |
| - | [[Category: | + | [[Category: Phosphotransferase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 22:14:24 2008'' | |
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Revision as of 19:14, 4 May 2008
CRYSTAL STRUCTURE OF YEAST THYMIDYLATE KINASE COMPLEXED WITH THE BISUBSTRATE INHIBITOR TP5A AT 2.0 A RESOLUTION: IMPLICATIONS FOR CATALYSIS AND AZT ACTIVATION
Overview
The crystal structure of yeast thymidylate kinase (TmpK) complexed with the bisubstrate inhibitor P1-(5'-adenosyl) P5-(5'-thymidyl) pentaphosphate (TP5A) was determined at 2.0 A resolution. In this complex, TmpK adopts a closed conformation with a region (LID) of the protein closing upon the substrate and forming a helix. The interactions of TmpK and TP5A strongly suggest that arginine 15, which is located in the phosphate binding loop (P-loop) sequence, plays a catalytic role by interacting with an oxygen atom of the transferred phosphoryl group. Unlike other nucleoside monophosphate kinases where basic residues from the LID region participate in stabilizing the transition state, TmpK lacks such residues in the LID region. We attribute this function to Arg 15 of the P-loop. TmpK plays an important role in the phosphorylation of the AIDS prodrug AZT. The structures of TmpK with dTMP and with AZT-MP [Lavie, A., et al. (1997) Nat. Struct. Biol. 4, 601-604] implicate the movement of Arg15 in response to AZT-MP binding as an important factor in the 200-fold reduced catalytic rate with AZT-MP. TmpK from Escherichia coli lacks this arginine in its P-loop while having basic residues in the LID region. This suggested that, if such a P-loop movement were to occur in the E. coli TmpK upon AZT-MP binding, it should not have such a detrimental effect on catalysis. This hypothesis was tested, and as postulated, E. coli TmpK phosphorylates AZT-MP only 2.5 times slower than dTMP.
About this Structure
3TMK is a Single protein structure of sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.
Reference
Crystal structure of yeast thymidylate kinase complexed with the bisubstrate inhibitor P1-(5'-adenosyl) P5-(5'-thymidyl) pentaphosphate (TP5A) at 2.0 A resolution: implications for catalysis and AZT activation., Lavie A, Konrad M, Brundiers R, Goody RS, Schlichting I, Reinstein J, Biochemistry. 1998 Mar 17;37(11):3677-86. PMID:9521686 Page seeded by OCA on Sun May 4 22:14:24 2008
