1dd6: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older editNewer edit →
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
Line 1: Line 1:
[[Image:1dd6.jpg|left|200px]]
{{Seed}}
[[Image:1dd6.png|left|200px]]


<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1dd6|  PDB=1dd6  |  SCENE=  }}  
{{STRUCTURE_1dd6|  PDB=1dd6  |  SCENE=  }}  


'''IMP-1 METALLO BETA-LACTAMASE FROM PSEUDOMONAS AERUGINOSA IN COMPLEX WITH A MERCAPTOCARBOXYLATE INHIBITOR'''
===IMP-1 METALLO BETA-LACTAMASE FROM PSEUDOMONAS AERUGINOSA IN COMPLEX WITH A MERCAPTOCARBOXYLATE INHIBITOR===




==Overview==
<!--  
Metallo beta-lactamase enzymes confer antibiotic resistance to bacteria by catalyzing the hydrolysis of beta-lactam antibiotics. This relatively new form of resistance is spreading unchallenged as there is a current lack of potent and selective inhibitors of metallo beta-lactamases. Reported here are the crystal structures of the native IMP-1 metallo beta-lactamase from Pseudomonas aeruginosa and its complex with a mercaptocarboxylate inhibitor, 2-[5-(1-tetrazolylmethyl)thien-3-yl]-N-[2-(mercaptomethyl)-4 -(phenylb utyrylglycine)]. The structures were determined by molecular replacement, and refined to 3.1 A (native) and 2.0 A (complex) resolution. Binding of the inhibitor in the active site induces a conformational change that results in closing of the flap and transforms the active site groove into a tunnel-shaped cavity enclosing 83% of the solvent accessible surface area of the inhibitor. The inhibitor binds in the active site through interactions with residues that are conserved among metallo beta-lactamases; the inhibitor's carboxylate group interacts with Lys161, and the main chain amide nitrogen of Asn167. In the "oxyanion hole", the amide carbonyl oxygen of the inhibitor interacts through a water molecule with the side chain of Asn167, the inhibitor's thiolate bridges the two Zn(II) ions in the active site displacing the bridging water, and the phenylbutyryl side chain binds in a hydrophobic pocket (S1) at the base of the flap. The flap is displaced 2.9 A compared to the unbound structure, allowing Trp28 to interact edge-to-face with the inhibitor's thiophene ring. The similarities between this inhibitor and the beta-lactam substrates suggest a mode of substrate binding and the role of the conserved residues in the active site. It appears that the metallo beta-lactamases bind their substrates by establishing a subset of binding interactions near the catalytic center with conserved characteristic chemical groups of the beta-lactam substrates. These interactions are complemented by additional nonspecific binding between the more variable groups in the substrates and the flexible flap. This unique mode of binding of the mercaptocarboxylate inhibitor in the enzyme active site provides a binding model for metallo beta-lactamase inhibition with utility for future drug design.
The line below this paragraph, {{ABSTRACT_PUBMED_10757977}}, adds the Publication Abstract to the page
(as it appears on PubMed at http://www.pubmed.gov), where 10757977 is the PubMed ID number.
-->
{{ABSTRACT_PUBMED_10757977}}


==About this Structure==
==About this Structure==
Line 38: Line 42:
[[Category: Mercaptocarboxylate inhibitor]]
[[Category: Mercaptocarboxylate inhibitor]]
[[Category: Metallo beta-lactamase inhibitor]]
[[Category: Metallo beta-lactamase inhibitor]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 13:42:55 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 22:50:54 2008''

Revision as of 19:50, 30 June 2008

File:1dd6.png

Template:STRUCTURE 1dd6

IMP-1 METALLO BETA-LACTAMASE FROM PSEUDOMONAS AERUGINOSA IN COMPLEX WITH A MERCAPTOCARBOXYLATE INHIBITOR

Template:ABSTRACT PUBMED 10757977

About this Structure

1DD6 is a Single protein structure of sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA.

Reference

Crystal structure of the IMP-1 metallo beta-lactamase from Pseudomonas aeruginosa and its complex with a mercaptocarboxylate inhibitor: binding determinants of a potent, broad-spectrum inhibitor., Concha NO, Janson CA, Rowling P, Pearson S, Cheever CA, Clarke BP, Lewis C, Galleni M, Frere JM, Payne DJ, Bateson JH, Abdel-Meguid SS, Biochemistry. 2000 Apr 18;39(15):4288-98. PMID:10757977

Page seeded by OCA on Mon Jun 30 22:50:54 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "https://proteopedia.org/index.php?title=1dd6&oldid=586869"