4gt9: Difference between revisions
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[[ | ==T. Maritima FDTS with FAD, dUMP and Folate.== | ||
<StructureSection load='4gt9' size='340' side='right' caption='[[4gt9]], [[Resolution|resolution]] 1.39Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4gt9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Thermotoga_maritima_msb8 Thermotoga maritima msb8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GT9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GT9 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=MEF:N-({4-[(6AR)-3-AMINO-1-OXO-1,2,5,6,6A,7-HEXAHYDROIMIDAZO[1,5-F]PTERIDIN-8(9H)-YL]PHENYL}CARBONYL)-L-GLUTAMIC+ACID'>MEF</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</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 Thermotoga maritima MSB8])</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=4gt9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gt9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gt9 RCSB], [http://www.ebi.ac.uk/pdbsum/4gt9 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The 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<ref>PMID:23019356</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | |||
*[[Thymidylate synthase|Thymidylate synthase]] | |||
== | == References == | ||
[[ | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Thermotoga maritima msb8]] | [[Category: Thermotoga maritima msb8]] | ||
[[Category: Kohen, A | [[Category: Kohen, A]] | ||
[[Category: Lesley, S A | [[Category: Lesley, S A]] | ||
[[Category: Mathews, I I | [[Category: Mathews, I I]] | ||
[[Category: 10-methylenetetrahydrofolate]] | [[Category: 10-methylenetetrahydrofolate]] | ||
[[Category: Dump]] | [[Category: Dump]] | ||
Revision as of 12:51, 10 December 2014
T. Maritima FDTS with FAD, dUMP and Folate.T. Maritima FDTS with FAD, dUMP and Folate.
Structural highlights
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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