1nmx: Difference between revisions
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|PDB= 1nmx |SIZE=350|CAPTION= <scene name='initialview01'>1nmx</scene>, resolution 1.7Å | |PDB= 1nmx |SIZE=350|CAPTION= <scene name='initialview01'>1nmx</scene>, resolution 1.7Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <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> | ||
|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] | |ACTIVITY= <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> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1nmx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nmx OCA], [http://www.ebi.ac.uk/pdbsum/1nmx PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1nmx RCSB]</span> | |||
}} | }} | ||
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[[Category: Segura-Pena, D.]] | [[Category: Segura-Pena, D.]] | ||
[[Category: Veit, T.]] | [[Category: Veit, T.]] | ||
[[Category: fluorothymidine]] | [[Category: fluorothymidine]] | ||
[[Category: p-loop]] | [[Category: p-loop]] | ||
[[Category: thymidylate kinase]] | [[Category: thymidylate kinase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:32:37 2008'' | ||
Revision as of 22:32, 30 March 2008
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| , resolution 1.7Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Activity: | dTMP kinase, with EC number 2.7.4.9 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of human thymidylate kinase with FLTMP and ADP
OverviewOverview
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 StructureAbout this Structure
1NMX is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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
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