This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


1jak

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1jak.gif|left|200px]]
+
{{Seed}}
 +
[[Image:1jak.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1jak| PDB=1jak | SCENE= }}
{{STRUCTURE_1jak| PDB=1jak | SCENE= }}
-
'''Streptomyces plicatus beta-N-acetylhexosaminidase in Complex with (2R,3R,4S,5R)-2-acetamido-3,4-dihydroxy-5-hydroxymethyl-piperidinium chloride (IFG)'''
+
===Streptomyces plicatus beta-N-acetylhexosaminidase in Complex with (2R,3R,4S,5R)-2-acetamido-3,4-dihydroxy-5-hydroxymethyl-piperidinium chloride (IFG)===
-
==Overview==
+
<!--
-
Azasugar inhibitors of the isofagomine class are potent competitive inhibitors of configuration-retaining beta-glycosidases. This potency results from the formation of a strong electrostatic interaction between a protonated endocyclic nitrogen at the "anomeric" center of the inhibitor and the catalytic nucleophile of the enzyme. Although the majority of retaining beta-glycosidases use a mechanism involving a carboxylate residue as a nucleophile, Streptomyces plicatus beta-N-acetylhexos-aminidase (SpHEX) and related family 20 glycosidases lack such a catalytic residue and use instead the carbonyl oxygen of the 2-acetamido group of the substrate as a nucleophile to "attack" the anomeric center. Thus, a strong electrostatic interaction between the inhibitor and enzyme is not expected to occur; nonetheless, the 1-N-azasugar (2R,3R,4S,5R)-2-acetamido-3,4-dihydroxy-5-hydroxymethyl-piperidinium hydrochloride (GalNAc-isofagomine.HCl), which was synthesized and assayed for its ability to inhibit SpHEX, was found to be a potent competitive inhibitor of the enzyme (K(i) = 2.7 microm). A crystallographic complex of GalNAc-isofagomine bound to SpHEX was solved and refined to 1.75 A and revealed that the lack of a strong electrostatic interaction between the "anomeric" center of GalNAc-isofagomine and SpHEX is compensated for by a novel 2.8-A hydrogen bond formed between the equatorial proton of the endocyclic nitrogen of the azasugar ring and the carboxylate of the general acid-base residue Glu-314 of SpHEX. This interaction appears to contribute to the unexpected potency of GalNAc-isofagomine toward SpHEX.
+
The line below this paragraph, {{ABSTRACT_PUBMED_11522797}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 11522797 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_11522797}}
==About this Structure==
==About this Structure==
Line 35: Line 39:
[[Category: Isofagomine inhibitor complex]]
[[Category: Isofagomine inhibitor complex]]
[[Category: Substrate-assisted catalysis]]
[[Category: Substrate-assisted catalysis]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 20:59:02 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 16:59:59 2008''

Revision as of 15:35, 1 July 2008

Image:1jak.png

Template:STRUCTURE 1jak

Streptomyces plicatus beta-N-acetylhexosaminidase in Complex with (2R,3R,4S,5R)-2-acetamido-3,4-dihydroxy-5-hydroxymethyl-piperidinium chloride (IFG)

Template:ABSTRACT PUBMED 11522797

About this Structure

1JAK is a Single protein structure of sequence from Streptomyces plicatus. Full crystallographic information is available from OCA.

Reference

Biochemical and structural assessment of the 1-N-azasugar GalNAc-isofagomine as a potent family 20 beta-N-acetylhexosaminidase inhibitor., Mark BL, Vocadlo DJ, Zhao D, Knapp S, Withers SG, James MN, J Biol Chem. 2001 Nov 9;276(45):42131-7. Epub 2001 Aug 24. PMID:11522797

Page seeded by OCA on Tue Jul 1 16:59:59 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

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