1vza
From Proteopedia
(New page: 200px<br /><applet load="1vza" size="450" color="white" frame="true" align="right" spinBox="true" caption="1vza, resolution 2.5Å" /> '''THYMIDYLATE SYNTHASE ...) |
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| - | [[Image:1vza.gif|left|200px]]<br /><applet load="1vza" size=" | + | [[Image:1vza.gif|left|200px]]<br /><applet load="1vza" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1vza, resolution 2.5Å" /> | caption="1vza, resolution 2.5Å" /> | ||
'''THYMIDYLATE SYNTHASE E60D MUTANT BINARY COMPLEX WITH 2'-DEOXYURIDINE 5'-MONOPHOSPHATE (DUMP)'''<br /> | '''THYMIDYLATE SYNTHASE E60D MUTANT BINARY COMPLEX WITH 2'-DEOXYURIDINE 5'-MONOPHOSPHATE (DUMP)'''<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== | ||
| - | 1VZA 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 as [http://en.wikipedia.org/wiki/ligand ligand]. 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:// | + | 1VZA 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> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1VZA 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: UMP]] | [[Category: UMP]] | ||
[[Category: methyltransferase]] | [[Category: methyltransferase]] | ||
[[Category: nucleotide synthase]] | [[Category: nucleotide synthase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:38:51 2008'' |
Revision as of 13:38, 21 February 2008
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THYMIDYLATE SYNTHASE E60D MUTANT BINARY COMPLEX WITH 2'-DEOXYURIDINE 5'-MONOPHOSPHATE (DUMP)
Overview
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
1VZA is a Single protein structure of sequence from Lactobacillus casei with as ligand. Active as Thymidylate synthase, with EC number 2.1.1.45 Full crystallographic information is available from OCA.
Reference
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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