1nn5: Difference between revisions

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<StructureSection load='1nn5' size='340' side='right'caption='[[1nn5]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
<StructureSection load='1nn5' size='340' side='right'caption='[[1nn5]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1nn5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NN5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NN5 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1nn5]] 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=1NN5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NN5 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/dTMP_kinase dTMP kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.9 2.7.4.9] </span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1nn5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nn5 OCA], [https://pdbe.org/1nn5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nn5 RCSB], [https://www.ebi.ac.uk/pdbsum/1nn5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nn5 ProSAT]</span></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=1nn5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nn5 OCA], [https://pdbe.org/1nn5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nn5 RCSB], [https://www.ebi.ac.uk/pdbsum/1nn5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nn5 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/KTHY_HUMAN KTHY_HUMAN]] Catalyzes the conversion of dTMP to dTDP.  
[https://www.uniprot.org/uniprot/KTHY_HUMAN KTHY_HUMAN] Catalyzes the conversion of dTMP to dTDP.
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</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=1nn5 ConSurf].
</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=1nn5 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== 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.
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:12614151<ref>PMID:12614151</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1nn5" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Thymidylate kinase 3D structures|Thymidylate kinase 3D structures]]
*[[Thymidylate kinase 3D structures|Thymidylate kinase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[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: D4tmp]]
[[Category: P-loop]]
[[Category: Thymidylate kinase]]
[[Category: Transferase]]

Latest revision as of 10:57, 14 February 2024

Crystal structure of human thymidylate kinase with d4TMP + AppNHpCrystal structure of human thymidylate kinase with d4TMP + AppNHp

Structural highlights

1nn5 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 1.5Å
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

1nn5, resolution 1.50Å

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