1vze: Difference between revisions
New page: left|200px<br /><applet load="1vze" size="450" color="white" frame="true" align="right" spinBox="true" caption="1vze, resolution 2.3Å" /> '''L. CASEI THYMIDYLATE ... |
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[[Image:1vze.jpg|left|200px]]<br /><applet load="1vze" size=" | [[Image:1vze.jpg|left|200px]]<br /><applet load="1vze" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1vze, resolution 2.3Å" /> | caption="1vze, resolution 2.3Å" /> | ||
'''L. CASEI THYMIDYLATE SYNTHASE MUTANT E60Q TERNARY COMPLEX WITH DUMP AND CB3717'''<br /> | '''L. CASEI THYMIDYLATE SYNTHASE MUTANT E60Q TERNARY COMPLEX WITH DUMP AND CB3717'''<br /> | ||
==Overview== | ==Overview== | ||
Three steps along the pathway of binding, orientation of substrates and | 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 Structure== | ==About this Structure== | ||
1VZE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Lactobacillus_casei Lactobacillus casei] with UMP and CB3 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | 1VZE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Lactobacillus_casei Lactobacillus casei] with <scene name='pdbligand=UMP:'>UMP</scene> and <scene name='pdbligand=CB3:'>CB3</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VZE OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Thymidylate synthase]] | [[Category: Thymidylate synthase]] | ||
[[Category: Birdsall, D | [[Category: Birdsall, D L.]] | ||
[[Category: Finer-Moore, J.]] | [[Category: Finer-Moore, J.]] | ||
[[Category: Stroud, R | [[Category: Stroud, R M.]] | ||
[[Category: CB3]] | [[Category: CB3]] | ||
[[Category: UMP]] | [[Category: UMP]] | ||
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[[Category: nucleotide synthase]] | [[Category: nucleotide synthase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:38:56 2008'' | ||
Revision as of 16:38, 21 February 2008
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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 with and as ligands. Active as Thymidylate synthase, with EC number 2.1.1.45 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
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