We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

2g89

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:2g89.gif|left|200px]]
+
{{Seed}}
 +
[[Image:2g89.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2g89| PDB=2g89 | SCENE= }}
{{STRUCTURE_2g89| PDB=2g89 | SCENE= }}
-
'''L. casei thymidylate synthase Y261A in complex with substrate, dUMP'''
+
===L. casei thymidylate synthase Y261A in complex with substrate, dUMP===
-
==Overview==
+
<!--
-
The enzyme thymidylate synthase (TS) catalyzes the reductive methylation of 2'-deoxyuridine 5'-monophosphate (dUMP) to 2'-deoxythymidine 5'-monophosphate. Using kinetic and X-ray crystallography experiments, we have examined the role of the highly conserved Tyr-261 in the catalytic mechanism of TS. While Tyr-261 is distant from the site of methyl transfer, mutants at this position show a marked decrease in enzymatic activity. Given that Tyr-261 forms a hydrogen bond with the dUMP 3'-O, we hypothesized that this interaction would be important for substrate binding, orientation, and specificity. Our results, surprisingly, show that Tyr-261 contributes little to these features of the mechanism of TS. However, the residue is part of the structural core of closed ternary complexes of TS, and conservation of the size and shape of the Tyr side chain is essential for maintaining wild-type values of kcat/Km. Moderate increases in Km values for both the substrate and cofactor upon mutation of Tyr-261 arise mainly from destabilization of the active conformation of a loop containing a dUMP-binding arginine. Besides binding dUMP, this loop has a key role in stabilizing the closed conformation of the enzyme and in shielding the active site from the bulk solvent during catalysis. Changes to atomic vibrations in crystals of a ternary complex of Escherichia coli Tyr261Trp are associated with a greater than 2000-fold drop in kcat/Km. These results underline the important contribution of dynamics to catalysis in TS.
+
The line below this paragraph, {{ABSTRACT_PUBMED_16768437}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 16768437 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_16768437}}
==About this Structure==
==About this Structure==
Line 31: Line 35:
[[Category: Dump-binding residue]]
[[Category: Dump-binding residue]]
[[Category: Transferase]]
[[Category: Transferase]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu May 22 22:23:08 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 00:48:35 2008''

Revision as of 21:48, 28 July 2008

Image:2g89.png

Template:STRUCTURE 2g89

L. casei thymidylate synthase Y261A in complex with substrate, dUMP

Template:ABSTRACT PUBMED 16768437

About this Structure

2G89 is a Single protein structure of sequence from Lactobacillus casei. Full crystallographic information is available from OCA.

Reference

The role of protein dynamics in thymidylate synthase catalysis: variants of conserved 2'-deoxyuridine 5'-monophosphate (dUMP)-binding Tyr-261., Newby Z, Lee TT, Morse RJ, Liu Y, Liu L, Venkatraman P, Santi DV, Finer-Moore JS, Stroud RM, Biochemistry. 2006 Jun 20;45(24):7415-28. PMID:16768437

Page seeded by OCA on Tue Jul 29 00:48:35 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2g89"
Personal tools