6ojs: Difference between revisions
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New page: '''Unreleased structure''' The entry 6ojs is ON HOLD until Paper Publication Authors: Czyzyk, D.J., Anderson, K.S., Jorgensen, W.L., Valhondo, M. Description: Crystal structure of TS-D... |
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==Crystal structure of TS-DHFR from Cryptosporidium hominis in complex with NADPH, FdUMP, MTX and 2-amino-4-oxo-4,7-dihydro-pyrrolo[2,3-d]pyrimidine-methyl-phenyl-D-glutamic acid== | |||
<StructureSection load='6ojs' size='340' side='right'caption='[[6ojs]], [[Resolution|resolution]] 3.21Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6ojs]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryptosporidium_hominis Cryptosporidium hominis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OJS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OJS 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]] 3.214Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D96:N-{4-[(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]benzene-1-carbonyl}-D-glutamic+acid'>D96</scene>, <scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=UFP:5-FLUORO-2-DEOXYURIDINE-5-MONOPHOSPHATE'>UFP</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=6ojs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ojs OCA], [https://pdbe.org/6ojs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ojs RCSB], [https://www.ebi.ac.uk/pdbsum/6ojs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ojs ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A0S4TER9_CRYHO A0A0S4TER9_CRYHO] Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism.[PIRNR:PIRNR000389] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Thymidylate synthase (TS), found in all organisms, is an essential enzyme responsible for the de novo synthesis of deoxythymidine monophosphate. The TS active sites of the protozoal parasite Cryptosporidium hominis and human are relatively conserved. Evaluation of antifolate compound 1 and its R-enantiomer 2 against both enzymes reveals divergent inhibitor selectivity and enzyme stereospecificity. To establish how C. hominis and human TS (ChTS and hTS) selectively discriminate 1 and 2, respectively, we determined crystal structures of ChTS complexed with 2 and hTS complexed with 1 or 2. Coupled with the previously determined structure of ChTS complexed with 1, we discuss a possible mechanism for enzyme stereospecificity and inhibitor selectivity. This article is protected by copyright. All rights reserved. | |||
Understanding the Structural Basis of Species Selective, Stereospecific Inhibition for Cryptosporidium and Human Thymidylate Synthase.,Czyzyk DJ, Valhondo M, Jorgensen WL, Anderson KS FEBS Lett. 2019 Jun 7. doi: 10.1002/1873-3468.13474. PMID:31172516<ref>PMID:31172516</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6ojs" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Cryptosporidium hominis]] | |||
[[Category: Large Structures]] | |||
[[Category: Anderson KS]] | |||
[[Category: Czyzyk DJ]] | |||
[[Category: Jorgensen WL]] | |||
[[Category: Valhondo M]] | |||
Latest revision as of 10:11, 11 October 2023
Crystal structure of TS-DHFR from Cryptosporidium hominis in complex with NADPH, FdUMP, MTX and 2-amino-4-oxo-4,7-dihydro-pyrrolo[2,3-d]pyrimidine-methyl-phenyl-D-glutamic acidCrystal structure of TS-DHFR from Cryptosporidium hominis in complex with NADPH, FdUMP, MTX and 2-amino-4-oxo-4,7-dihydro-pyrrolo[2,3-d]pyrimidine-methyl-phenyl-D-glutamic acid
Structural highlights
FunctionA0A0S4TER9_CRYHO Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism.[PIRNR:PIRNR000389] Publication Abstract from PubMedThymidylate synthase (TS), found in all organisms, is an essential enzyme responsible for the de novo synthesis of deoxythymidine monophosphate. The TS active sites of the protozoal parasite Cryptosporidium hominis and human are relatively conserved. Evaluation of antifolate compound 1 and its R-enantiomer 2 against both enzymes reveals divergent inhibitor selectivity and enzyme stereospecificity. To establish how C. hominis and human TS (ChTS and hTS) selectively discriminate 1 and 2, respectively, we determined crystal structures of ChTS complexed with 2 and hTS complexed with 1 or 2. Coupled with the previously determined structure of ChTS complexed with 1, we discuss a possible mechanism for enzyme stereospecificity and inhibitor selectivity. This article is protected by copyright. All rights reserved. Understanding the Structural Basis of Species Selective, Stereospecific Inhibition for Cryptosporidium and Human Thymidylate Synthase.,Czyzyk DJ, Valhondo M, Jorgensen WL, Anderson KS FEBS Lett. 2019 Jun 7. doi: 10.1002/1873-3468.13474. PMID:31172516[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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