4gtl: Difference between revisions
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==T. Maritima FDTS (R174K mutant) with FAD== | ==T. Maritima FDTS (R174K mutant) with FAD== | ||
<StructureSection load='4gtl' size='340' side='right' caption='[[4gtl]], [[Resolution|resolution]] 2.17Å' scene=''> | <StructureSection load='4gtl' size='340' side='right' caption='[[4gtl]], [[Resolution|resolution]] 2.17Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4gtl]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[4gtl]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Thema Thema]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GTL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GTL FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">thyX, thy1, TM_0449 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=243274 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">thyX, thy1, 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=4gtl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gtl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gtl RCSB], [http://www.ebi.ac.uk/pdbsum/4gtl 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=4gtl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gtl OCA], [http://pdbe.org/4gtl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gtl RCSB], [http://www.ebi.ac.uk/pdbsum/4gtl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gtl ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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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 4gtl" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Thema]] | ||
[[Category: Kohen, A]] | [[Category: Kohen, A]] | ||
[[Category: Lesley, S A]] | [[Category: Lesley, S A]] | ||
Revision as of 04:07, 5 August 2016
T. Maritima FDTS (R174K mutant) with FADT. Maritima FDTS (R174K mutant) with FAD
Structural highlights
Function[THYX_THEMA] Catalyzes the formation of dTMP and tetrahydrofolate from dUMP and methylenetetrahydrofolate. Publication Abstract from PubMedThe DNA nucleotide thymidylate is synthesized by the enzyme thymidylate synthase, which catalyzes the reductive methylation of deoxyuridylate using the cofactor methylene-tetrahydrofolate (CH(2)H(4)folate). Most organisms, including humans, rely on the thyA- or TYMS-encoded classic thymidylate synthase, whereas, certain microorganisms, including all Rickettsia and other pathogens, use an alternative thyX-encoded flavin-dependent thymidylate synthase (FDTS). Although several crystal structures of FDTSs have been reported, the absence of a structure with folates limits understanding of the molecular mechanism and the scope of drug design for these enzymes. Here we present X-ray crystal structures of FDTS with several folate derivatives, which together with mutagenesis, kinetic analysis, and computer modeling shed light on the cofactor binding and function. The unique structural data will likely facilitate further elucidation of FDTSs' mechanism and the design of structure-based inhibitors as potential leads to new antimicrobial drugs. Folate binding site of flavin-dependent thymidylate synthase.,Koehn EM, Perissinotti LL, Moghram S, Prabhakar A, Lesley SA, Mathews II, Kohen A Proc Natl Acad Sci U S A. 2012 Sep 25;109(39):15722-7. Epub 2012 Sep 10. PMID:23019356[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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