View source for 3tmk


==CRYSTAL STRUCTURE OF YEAST THYMIDYLATE KINASE COMPLEXED WITH THE BISUBSTRATE INHIBITOR TP5A AT 2.0 A RESOLUTION: IMPLICATIONS FOR CATALYSIS AND AZT ACTIVATION==
<StructureSection load='3tmk' size='340' side='right'caption='[[3tmk]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3tmk]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TMK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TMK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=T5A:P1-(5-ADENOSYL)P5-(5-THYMIDYL)PENTAPHOSPHATE'>T5A</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3tmk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tmk OCA], [https://pdbe.org/3tmk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tmk RCSB], [https://www.ebi.ac.uk/pdbsum/3tmk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tmk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/KTHY_YEAST KTHY_YEAST] Catalyzes the conversion of dTMP to dTDP.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/tm/3tmk_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3tmk ConSurf].
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== Publication Abstract from PubMed ==
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.

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<ref>PMID:9521686</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Thymidylate kinase 3D structures|Thymidylate kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Brundiers R]]
[[Category: Goody RS]]
[[Category: Konrad M]]
[[Category: Lavie A]]
[[Category: Reinstein J]]
[[Category: Schlichting I]]