View source for 5h38


==Structural analysis of KSHV thymidylate synthase==
<StructureSection load='5h38' size='340' side='right'caption='[[5h38]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5h38]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_gammaherpesvirus_8 Human gammaherpesvirus 8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5H38 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5H38 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]] 1.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=5h38 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h38 OCA], [https://pdbe.org/5h38 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5h38 RCSB], [https://www.ebi.ac.uk/pdbsum/5h38 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5h38 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TYSY_HHV8P TYSY_HHV8P] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Kaposi's sarcoma-associated herpesvirus (KSHV) is a highly infectious human herpesvirus that causes Kaposi's sarcoma. KSHV encodes functional thymidylate synthase, which is a target for anticancer drugs such as raltitrexed or 5-fluorouracil. Thymidylate synthase catalyzes the conversion of 2'-deoxyuridine-5'-monophosphate (dUMP) to thymidine-5'-monophosphate (dTMP) using 5,10-methylenetetrahydrofolate (mTHF) as a co-substrate. The crystal structures of thymidylate synthase from KSHV (apo), complexes with dUMP (binary), and complexes with both dUMP and raltitrexed (ternary) were determined at 1.7 A, 2.0 A, and 2.4 A, respectively. While the ternary complex structures of human thymidylate synthase and E. coli thymidylate synthase had a closed conformation, the ternary complex structure of KSHV thymidylate synthase was observed in an open conformation, similar to that of rat thymidylate synthase. The complex structures of KSHV thymidylate synthase did not have a covalent bond between the sulfhydryl group of Cys219 and C6 atom of dUMP, unlike the human thymidylate synthase. The catalytic Cys residue demonstrated a dual conformation in the apo structure, and its sulfhydryl group was oriented toward the C6 atom of dUMP with no covalent bond upon ligand binding in the complex structures. These structural data provide the potential use of antifolates such as raltitrexed as a viral induced anticancer drug and structural basis to design drugs for targeting the thymidylate synthase of KSHV.

Structural Analysis of Thymidylate Synthase from Kaposi's Sarcoma-Associated Herpesvirus with the Anticancer Drug Raltitrexed.,Choi YM, Yeo HK, Park YW, Lee JY PLoS One. 2016 Dec 9;11(12):e0168019. doi: 10.1371/journal.pone.0168019., eCollection 2016. PMID:27936107<ref>PMID:27936107</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5h38" style="background-color:#fffaf0;"></div>

==See Also==
*[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human gammaherpesvirus 8]]
[[Category: Large Structures]]
[[Category: Choi YM]]
[[Category: Lee JY]]
[[Category: Park YW]]
[[Category: Yeo HK]]