1vze: Difference between revisions

Revision as of 12:57, 3 May 2008

L. CASEI THYMIDYLATE SYNTHASE MUTANT E60Q TERNARY COMPLEX WITH DUMP AND CB3717

OverviewOverview

Three steps along the pathway of binding, orientation of substrates and release of products are revealed by X-ray crystallographic structures of ternary complexes of the wild-type Lactobacillus casei thymidylate synthase enzyme. Each complex was formed by diffusion of either the cofactor 5,10-methylene-5,6,7,8-tetrahydrofolate or the folate analog 10-propargyl-5,8-dideazafolate into binary co-crystals of thymidylate synthase with 2'-deoxyuridine-5'-monophosphate. A two-substrate/enzyme complex is formed where the substrates remain unaltered. The imidazolidine ring is unopened and the pterin of the 5,10-methylene-5,6,7,8-tetrahydrofolate cofactor binds at an unproductive "alternate" site. We propose that the presence of the pterin at this site may represent an initial interaction with the enzyme that precedes all catalytic events. The structure of the 2'-deoxyuridine-5'-monophosphate and 10-propargyl-5,8-dideazafolate folate analog complex identifies both ligands in orientations favorable for the initiation of catalysis and resembles the productive complex. A product complex where the ligands have been converted into products of the thymidylate synthase reaction within the crystal, 2'-deoxythymidine-5'-monophosphate and 7,8-dihydrofolate, shows how ligands are situated within the enzyme after catalysis and on the way to product release.

About this StructureAbout this Structure

1VZE is a Single protein structure of sequence from Lactobacillus casei. Full crystallographic information is available from OCA.

ReferenceReference

Entropy in bi-substrate enzymes: proposed role of an alternate site in chaperoning substrate into, and products out of, thymidylate synthase., Birdsall DL, Finer-Moore J, Stroud RM, J Mol Biol. 1996 Jan 26;255(3):522-35. PMID:8568895 Page seeded by OCA on Sat May 3 12:57:06 2008

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OCA

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 [[Image:1vze.jpg|left|200px]]
- {{Structure
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-|PDB= 1vze |SIZE=350|CAPTION= <scene name='initialview01'>1vze</scene>, resolution 2.3&Aring;
+The line below this paragraph, containing "STRUCTURE_1vze", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=CB3:10-PROPARGYL-5,8-DIDEAZAFOLIC+ACID'>CB3</scene>, <scene name='pdbligand=UMP:2&#39;-DEOXYURIDINE+5&#39;-MONOPHOSPHATE'>UMP</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= THYMIDYLATE SYNTHASE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1582 Lactobacillus casei])
+-->
-|DOMAIN=
+{{STRUCTURE_1vze|  PDB=1vze  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1vze FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vze OCA], [http://www.ebi.ac.uk/pdbsum/1vze PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1vze RCSB]</span>
-}}
 '''L. CASEI THYMIDYLATE SYNTHASE MUTANT E60Q TERNARY COMPLEX WITH DUMP AND CB3717'''
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 [[Category: Finer-Moore, J.]]
 [[Category: Stroud, R M.]]
-[[Category: methyltransferase]]
+[[Category: Methyltransferase]]
-[[Category: nucleotide synthase]]
+[[Category: Nucleotide synthase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 12:57:06 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:29:06 2008''