4kas: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal structure of FDTS from T. maritima mutant (H53D) with FAD and dUMP== | ==Crystal structure of FDTS from T. maritima mutant (H53D) with FAD and dUMP== | ||
<StructureSection load='4kas' size='340' side='right' caption='[[4kas]], [[Resolution|resolution]] 1.85Å' scene=''> | <StructureSection load='4kas' size='340' side='right' caption='[[4kas]], [[Resolution|resolution]] 1.85Å' scene=''> | ||
| Line 7: | Line 8: | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">thy1, thyX, tm0449, TM_0449 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=243274 THEMA])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">thy1, thyX, tm0449, TM_0449 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=243274 THEMA])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidylate_synthase_(FAD) Thymidylate synthase (FAD)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.148 2.1.1.148] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidylate_synthase_(FAD) Thymidylate synthase (FAD)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.148 2.1.1.148] </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=4kas FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kas OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4kas RCSB], [http://www.ebi.ac.uk/pdbsum/4kas PDBsum]</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=4kas FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kas OCA], [http://pdbe.org/4kas PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kas RCSB], [http://www.ebi.ac.uk/pdbsum/4kas PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kas ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| Line 19: | Line 20: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4kas" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Thymidylate synthase|Thymidylate synthase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 18:06, 5 August 2016
Crystal structure of FDTS from T. maritima mutant (H53D) with FAD and dUMPCrystal structure of FDTS from T. maritima mutant (H53D) with FAD and dUMP
Structural highlights
Function[THYX_THEMA] Catalyzes the formation of dTMP and tetrahydrofolate from dUMP and methylenetetrahydrofolate. Publication Abstract from PubMedThe identification of flavin-dependent thymidylate synthase (FDTS) as an essential enzyme and its occurrence in several pathogenic microbes opens opportunities for using FDTS enzyme as an excellent target for new antimicrobial drug discovery. In contrast to the human thymidylate synthase enzyme that utilizes methylene-tetrahydrofolate (CH2H4 folate) for the conversion of dUMP to dTMP, the microbial enzymes utilize an additional non-covalently bound FAD molecule for the hydride transfer from NAD(P)H. The structural and mechanistic differences between the human and microbial enzymes present an attractive opportunity for the design of antimicrobial compounds specific for the pathogens. We have determined the crystal structure of FDTS enzyme in complex with the methyl donor, CH2H4 folate. We describe here the structure of a FDTS mutant and compare it with other FDTS complex structures, including a FDTS-CH2H4 folate complex. We identified a conformational change essential for substrate binding and propose a strategy for the design of FDTS specific inhibitors. Flavin-Dependent Thymidylate Synthase as a Drug Target for Deadly Microbes: Mutational Study and a Strategy for Inhibitor Design.,Mathews II J Bioterror Biodef. 2013 Apr 20;Suppl 12:004. PMID:24563811[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||||||