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.

1kzi

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1kzi.gif|left|200px]]
+
{{Seed}}
 +
[[Image:1kzi.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1kzi| PDB=1kzi | SCENE= }}
{{STRUCTURE_1kzi| PDB=1kzi | SCENE= }}
-
'''Crystal Structure of EcTS/dUMP/THF Complex'''
+
===Crystal Structure of EcTS/dUMP/THF Complex===
-
==Overview==
+
<!--
-
Mutant forms of thymidylate synthase (TS) with substitutions at the conserved active site residue, Trp 80, are deficient in the hydride transfer step of the TS reaction. These mutants produce a beta-mercaptoethanol (beta-ME) adduct of the 2'-deoxyuridine-5'-monophosphate (dUMP) exocyclic methylene intermediate. Trp 80 has been proposed to assist hydride transfer by stabilizing a 5,6,7,8-tetrahydrofolate (THF) radical cation intermediate [Barrett, J. E., Lucero, C. M., and Schultz, P. G. (1999) J. Am. Chem. Soc. 121, 7965-7966.] formed after THF changes its binding from the cofactor pocket to a putative alternate site. To understand the molecular basis of hydride transfer deficiency in a mutant in which Trp 80 was changed to Gly, we determined the X-ray structures of this mutant Escherichia coli TS complexed with dUMP and the folate analogue 10-propargyl-5,8-dideazafolate (CB3717) and of the wild-type enzyme complexed with dUMP and THF. The mutant enzyme has a cavity in the active site continuous with bulk solvent. This cavity, sealed from bulk solvent in wild-type TS by Leu 143, would allow nucleophilic attack of beta-ME on the dUMP C5 exocyclic methylene. The structure of the wild-type enzyme/dUMP/THF complex shows that THF is bound in the cofactor binding pocket and is well positioned to transfer hydride to the dUMP exocyclic methylene. Together, these results suggest that THF does not reorient during hydride transfer and indicate that the role of Trp 80 may be to orient Leu 143 to shield the active site from bulk solvent and to optimally position the cofactor for hydride transfer.
+
The line below this paragraph, {{ABSTRACT_PUBMED_12033935}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 12033935 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_12033935}}
==About this Structure==
==About this Structure==
Line 28: Line 32:
[[Category: Stroud, R M.]]
[[Category: Stroud, R M.]]
[[Category: Enzyme substrate complex]]
[[Category: Enzyme substrate complex]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 23:21:51 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 11:21:56 2008''

Revision as of 08:21, 2 July 2008

Image:1kzi.png

Template:STRUCTURE 1kzi

Crystal Structure of EcTS/dUMP/THF Complex

Template:ABSTRACT PUBMED 12033935

About this Structure

1KZI is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

Reference

Tryptophan 80 and leucine 143 are critical for the hydride transfer step of thymidylate synthase by controlling active site access., Fritz TA, Liu L, Finer-Moore JS, Stroud RM, Biochemistry. 2002 Jun 4;41(22):7021-9. PMID:12033935

Page seeded by OCA on Wed Jul 2 11:21:56 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1kzi"
Personal tools