2gyi

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:2gyi.jpg|left|200px]]
+
{{Seed}}
 +
[[Image:2gyi.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2gyi| PDB=2gyi | SCENE= }}
{{STRUCTURE_2gyi| PDB=2gyi | SCENE= }}
-
'''DESIGN, SYNTHESIS, AND CHARACTERIZATION OF A POTENT XYLOSE ISOMERASE INHIBITOR, D-THREONOHYDROXAMIC ACID, AND HIGH-RESOLUTION X-RAY CRYSTALLOGRAPHIC STRUCTURE OF THE ENZYME-INHIBITOR COMPLEX'''
+
===DESIGN, SYNTHESIS, AND CHARACTERIZATION OF A POTENT XYLOSE ISOMERASE INHIBITOR, D-THREONOHYDROXAMIC ACID, AND HIGH-RESOLUTION X-RAY CRYSTALLOGRAPHIC STRUCTURE OF THE ENZYME-INHIBITOR COMPLEX===
-
==Overview==
+
<!--
-
The binding of a potent inhibitor to the enzyme D-xylose isomerase from Streptomyces olivochromogenes was examined by kinetics and X-ray crystallography. The inhibitor D-threonohydroxamic acid (THA) was designed to mimic the putative transition state of the isomerization step catalyzed by the enzyme on the substrate xylose. THA was synthesized and found to be a slow-binding competitive inhibitor with the substrate glucose. The Ki &lt; or = 100 nM was at least one million-fold less than the KM for glucose. The X-ray crystallographic structure of xylose isomerase with THA soaked into the crystals (concentration = 1000Ki) was obtained to 1.6-A resolution and refined to an R factor of 21.6%. The free enzyme and the enzyme in the xylose isomerase-THA complex show no significant structural differences. THA binds in an analogous fashion to glucose, in a linear conformation, forming ligands with Mg-1 and Mg-2 and hydrogen bonds with His53 and Lys182. On the basis of these similarities to glucose binding and its potent inhibition, we propose that THA resembles the transition state for the enzyme-catalyzed hydride transfer reaction. The THA C2 hydroxyl forms a bridging ligand between Mg-1 and Mg-2; it must be deprotonated to do so. By analogy, we propose that, during the catalytic reaction, C2 of the substrate glucose is deprotonated, and that this proton can be moved to the C1 hydroxyl concomitant with hydride transfer. We find evidence for metal movement during catalysis upon deprotonation of the C2 hydroxyl, to allow formation of a bridging ligand.(ABSTRACT TRUNCATED AT 250 WORDS)
+
The line below this paragraph, {{ABSTRACT_PUBMED_7893671}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 7893671 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_7893671}}
==About this Structure==
==About this Structure==
Line 27: Line 31:
[[Category: Petsko, G A.]]
[[Category: Petsko, G A.]]
[[Category: Ringe, D.]]
[[Category: Ringe, D.]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:39:33 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 05:49:32 2008''

Revision as of 02:49, 29 July 2008

Image:2gyi.png

Template:STRUCTURE 2gyi

DESIGN, SYNTHESIS, AND CHARACTERIZATION OF A POTENT XYLOSE ISOMERASE INHIBITOR, D-THREONOHYDROXAMIC ACID, AND HIGH-RESOLUTION X-RAY CRYSTALLOGRAPHIC STRUCTURE OF THE ENZYME-INHIBITOR COMPLEX

Template:ABSTRACT PUBMED 7893671

About this Structure

2GYI is a Single protein structure of sequence from Streptomyces olivochromogenes. This structure supersedes the now removed PDB entry 1gyi. Full crystallographic information is available from OCA.

Reference

Design, synthesis, and characterization of a potent xylose isomerase inhibitor, D-threonohydroxamic acid, and high-resolution X-ray crystallographic structure of the enzyme-inhibitor complex., Allen KN, Lavie A, Petsko GA, Ringe D, Biochemistry. 1995 Mar 21;34(11):3742-9. PMID:7893671

Page seeded by OCA on Tue Jul 29 05:49:32 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

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