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[[Image:1nmx.gif|left|200px]]


{{Structure
==Crystal structure of human thymidylate kinase with FLTMP and ADP==
|PDB= 1nmx |SIZE=350|CAPTION= <scene name='initialview01'>1nmx</scene>, resolution 1.7&Aring;
<StructureSection load='1nmx' size='340' side='right'caption='[[1nmx]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=FDM:3'-FLUORO-3'-DEOXYTHYMIDINE+MONOPHOSPHATE'>FDM</scene> and <scene name='pdbligand=ADP:ADENOSINE-5'-DIPHOSPHATE'>ADP</scene>
<table><tr><td colspan='2'>[[1nmx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NMX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NMX FirstGlance]. <br>
|ACTIVITY= [http://en.wikipedia.org/wiki/dTMP_kinase dTMP kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.9 2.7.4.9]  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
|GENE=  
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=FDM:3-FLUORO-3-DEOXYTHYMIDINE+MONOPHOSPHATE'>FDM</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=1nmx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nmx OCA], [https://pdbe.org/1nmx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nmx RCSB], [https://www.ebi.ac.uk/pdbsum/1nmx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nmx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/KTHY_HUMAN KTHY_HUMAN] 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/nm/1nmx_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=1nmx ConSurf].
<div style="clear:both"></div>


'''Crystal structure of human thymidylate kinase with FLTMP and ADP'''
==See Also==
 
*[[Thymidylate kinase 3D structures|Thymidylate kinase 3D structures]]
 
__TOC__
==Overview==
</StructureSection>
Nucleoside analogue prodrugs are dependent on efficient intracellular stepwise phosphorylation to their triphosphate form to become therapeutically active. In many cases it is this activation pathway that largely determines the efficacy of the drug. To gain further understanding of the determinants for efficient conversion by the enzyme thymidylate kinase (TMPK) of clinically important thymidine monophosphate analogues to the corresponding diphosphates, we solved the crystal structures of the enzyme, with either ADP or the ATP analogue AppNHp at the phosphoryl donor site, in complex with TMP, AZTMP (previous work), NH2TMP, d4TMP, ddTMP, and FLTMP (this work) at the phosphoryl acceptor site. In conjunction with steady-state kinetic data, our structures shed light on the effect of 3'-substitutions in the nucleoside monophosphate (NMP) sugar moiety on the catalytic rate. We observe a direct correlation between the rate of phosphorylation of an NMP and its ability to induce a closing of the enzyme's phosphate-binding loop (P-loop). Our results show the drastic effects that slight modifications of the substrates exert on the enzyme's conformation and, hence, activity and suggest the type of substitutions that are compatible with efficient phosphorylation by TMPK.
 
==About this Structure==
1NMX is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NMX OCA].
 
==Reference==
Structures of human thymidylate kinase in complex with prodrugs: implications for the structure-based design of novel compounds., Ostermann N, Segura-Pena D, Meier C, Veit T, Monnerjahn C, Konrad M, Lavie A, Biochemistry. 2003 Mar 11;42(9):2568-77. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12614151 12614151]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: dTMP kinase]]
[[Category: Konrad M]]
[[Category: Konrad, M.]]
[[Category: Lavie A]]
[[Category: Lavie, A.]]
[[Category: Meier C]]
[[Category: Meier, C.]]
[[Category: Monnerjahn M]]
[[Category: Monnerjahn, M.]]
[[Category: Ostermann N]]
[[Category: Ostermann, N.]]
[[Category: Segura-Pena D]]
[[Category: Segura-Pena, D.]]
[[Category: Veit T]]
[[Category: Veit, T.]]
[[Category: ADP]]
[[Category: FDM]]
[[Category: MG]]
[[Category: fluorothymidine]]
[[Category: p-loop]]
[[Category: thymidylate kinase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:58:58 2008''

Latest revision as of 10:57, 14 February 2024

Crystal structure of human thymidylate kinase with FLTMP and ADPCrystal structure of human thymidylate kinase with FLTMP and ADP

Structural highlights

1nmx is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.7Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KTHY_HUMAN Catalyzes the conversion of dTMP to dTDP.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

1nmx, resolution 1.70Å

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