1tsn
From Proteopedia
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| - | [[Image:1tsn.jpg|left|200px]]<br /><applet load="1tsn" size=" | + | [[Image:1tsn.jpg|left|200px]]<br /><applet load="1tsn" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1tsn, resolution 2.2Å" /> | caption="1tsn, resolution 2.2Å" /> | ||
'''THYMIDYLATE SYNTHASE TERNARY COMPLEX WITH FDUMP AND METHYLENETETRAHYDROFOLATE'''<br /> | '''THYMIDYLATE SYNTHASE TERNARY COMPLEX WITH FDUMP AND METHYLENETETRAHYDROFOLATE'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1TSN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with PO4, UFP and C2F 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] Known structural/functional Site: <scene name='pdbsite=S1:Carboxy Modification At N1'>S1</scene>. Full crystallographic information is available from [http:// | + | 1TSN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=PO4:'>PO4</scene>, <scene name='pdbligand=UFP:'>UFP</scene> and <scene name='pdbligand=C2F:'>C2F</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] Known structural/functional Site: <scene name='pdbsite=S1:Carboxy+Modification+At+N1'>S1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TSN OCA]. |
==Reference== | ==Reference== | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:02:39 2008'' |
Revision as of 08:02, 3 February 2008
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THYMIDYLATE SYNTHASE TERNARY COMPLEX WITH FDUMP AND METHYLENETETRAHYDROFOLATE
Overview
Two crystal structures for E. coli thymidylate synthase (TS) bound to the, mechanism-based inhibitor 5-fluoro-dUMP (FdUMP) and, methylenetetrahydrofolate (CH2THF) have been determined to 2.6 and 2.2 A, nominal resolutions, with crystallographic R factors of 0.180 and 0.178, respectively. The inhibitor and cofactor are well ordered in both, structures and display covalent links to each other and to Cys 146 in the, TS active site. The structures are in general agreement with a previous, report for this complex (D. A. Matthews et al. (1990) J. Mol. Biol. 214, 937-948), but differ in two key respects: (i) the methylene bridge linking, FdUMP and CH2THF is rotated about 60 degrees to a different position and, (ii) the electron density for C6 of FdUMP, which is covalently linked to, Cys 146, is more diffuse than for the other atoms in the pyrimidine ring., The ligand arrangement observed in the previous structure led the authors, to propose that a large conformational change in ligand geometry must, occur in order to facilitate catalysis and yield the correct chirality in, the methyl of product dTMP. The new structures suggest a different, mechanism for product formation that does not require ligands to greatly, alter their conformations during catalysis and which makes use of, instability in the nucleotide-Cys 146 thiol adduct to avoid a deep free, energy well and assist in proton abstraction from dUMP. All intermediates, in the proposed mechanism were modeled and energy minimized in the TS, active site, and all can be accommodated in the present structures. The, role of ligand-induced conformational change in the TS mechanism and the, possibility of Tyr 94 acting as a base during catalysis are also, discussed.
About this Structure
1TSN is a Single protein structure of sequence from Escherichia coli with , and as ligands. Active as Thymidylate synthase, with EC number 2.1.1.45 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Use of strain in a stereospecific catalytic mechanism: crystal structures of Escherichia coli thymidylate synthase bound to FdUMP and methylenetetrahydrofolate., Hyatt DC, Maley F, Montfort WR, Biochemistry. 1997 Apr 15;36(15):4585-94. PMID:9109668
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