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.


1ong

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1ong.jpg|left|200px]]
+
{{Seed}}
 +
[[Image:1ong.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1ong| PDB=1ong | SCENE= }}
{{STRUCTURE_1ong| PDB=1ong | SCENE= }}
-
'''SHV-1 beta-lactamase with a penem inhibitor'''
+
===SHV-1 beta-lactamase with a penem inhibitor===
-
==Overview==
+
<!--
-
A new beta-lactamase inhibitor, a methylidene penem having a 5,6-dihydro-8H-imidazo[2,1-c][1,4]oxazine heterocyclic substituent at the C6 position with a Z configuration, irreversibly inhibits both class A and class C serine beta-lactamases with IC(50) values of 0.4 and 9.0 nM for TEM-1 and SHV-1 (class A), respectively, and 4.8 nM in AmpC (class C) beta-lactamases. The compound also inhibits irreversibly the class C extended-spectrum GC1 beta-lactamase (IC(50) = 6.2 nM). High-resolution crystallographic structures of a reaction intermediate of (5R)-(6Z)-6-(5,6-dihydro-8H-imidazo[2,1-c][1,4]oxazin-2-ylmethylene)-7-oxo -4-thia-1-azabicyclo[3.2.0]hept-2-ene-3-carboxylic acid 1 with the SHV-1 beta-lactamase and with the GC1 beta-lactamase have been determined by X-ray diffraction to resolutions of 1.10 and 1.38 A, respectively. The two complexes were refined to crystallographic R-factors (R(free)) of 0.141 (0.186) and 0.138 (0.202), respectively. Cryoquenching of the reaction of 1 with each beta-lactamase crystal produced a common, covalently bound intermediate. After acylation of the serine, a nucleophilic attack by the departing thiolate on the C6' atom yielded a novel seven-membered 1,4-thiazepine ring having R stereochemistry at the new C7 moiety. The orientation of this ring in each complex differs by a 180 degrees rotation about the bond to the acylated serine. The acyl ester bond is stabilized to hydrolysis through resonance stabilization with the dihydrothiazepine ring and by low occupancy or disorder of hydrolytic water molecules. In the class A complex, the buried water molecule on the alpha-face of the ester bond appears to be loosely bound or absent. In the class C complex, a water molecule on the beta-face is disordered and poorly activated for hydrolysis. Here, the acyl intermediate is unable to assist its own hydrolysis, as is thought to occur with many class C substrates.
+
The line below this paragraph, {{ABSTRACT_PUBMED_14609325}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 14609325 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_14609325}}
==About this Structure==
==About this Structure==
Line 31: Line 35:
[[Category: Drug design]]
[[Category: Drug design]]
[[Category: Penicillinase]]
[[Category: Penicillinase]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 04:03:53 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 11:00:22 2008''

Revision as of 08:00, 29 July 2008

Image:1ong.png

Template:STRUCTURE 1ong

SHV-1 beta-lactamase with a penem inhibitor

Template:ABSTRACT PUBMED 14609325

About this Structure

1ONG is a Single protein structure of sequence from Klebsiella pneumoniae. Full crystallographic information is available from OCA.

Reference

Inhibition of class A and class C beta-lactamases by penems: crystallographic structures of a novel 1,4-thiazepine intermediate., Nukaga M, Abe T, Venkatesan AM, Mansour TS, Bonomo RA, Knox JR, Biochemistry. 2003 Nov 18;42(45):13152-9. PMID:14609325

Page seeded by OCA on Tue Jul 29 11:00:22 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

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