1nn1

<StructureSection load='1nn1' size='340' side='right' caption='[[1nn1]], [[Resolution|resolution]] 1.90&Aring;' scene=''>

<table><tr><td colspan='2'>[[1nn1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NN1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1NN1 FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2DT:3-DEOXYTHYMIDINE-5-MONOPHOSPHATE'>2DT</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1nn1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nn1 OCA], [http://pdbe.org/1nn1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1nn1 RCSB], [http://www.ebi.ac.uk/pdbsum/1nn1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1nn1 ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/KTHY_HUMAN KTHY_HUMAN]] Catalyzes the conversion of dTMP to dTDP.

<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nn/1nn1_consurf.spt"</scriptWhenChecked>

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== Publication Abstract from PubMed ==

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.

 

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== References ==

[[Category: Human]]

[[Category: DTMP kinase]]

[[Category: Konrad, M]]

[[Category: Lavie, A]]

[[Category: Meier, C]]

[[Category: Monnerjahn, M]]

[[Category: Ostermann, N]]

[[Category: Segura-Pena, D]]

[[Category: Veit, T]]

[[Category: Transferase]]