1fr6
From Proteopedia
(New page: 200px<br /><applet load="1fr6" size="450" color="white" frame="true" align="right" spinBox="true" caption="1fr6, resolution 2.5Å" /> '''REFINED CRYSTAL STRUC...) |
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| - | [[Image:1fr6.gif|left|200px]]<br /><applet load="1fr6" size=" | + | [[Image:1fr6.gif|left|200px]]<br /><applet load="1fr6" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1fr6, resolution 2.5Å" /> | caption="1fr6, resolution 2.5Å" /> | ||
'''REFINED CRYSTAL STRUCTURE OF BETA-LACTAMASE FROM CITROBACTER FREUNDII INDICATES A MECHANISM FOR BETA-LACTAM HYDROLYSIS'''<br /> | '''REFINED CRYSTAL STRUCTURE OF BETA-LACTAMASE FROM CITROBACTER FREUNDII INDICATES A MECHANISM FOR BETA-LACTAM HYDROLYSIS'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Beta-Lactamases (EC 3.5.2.6, 'penicillinases') are a family of enzymes | + | Beta-Lactamases (EC 3.5.2.6, 'penicillinases') are a family of enzymes that protect bacteria against the lethal effects of cell-wall synthesis of penicillins, cephalosporins and related antibiotic agents, by hydrolysing the beta-lactam antibiotics to biologically inactive compounds. Their production can, therefore, greatly contribute to the clinical problem of antibiotic resistance. Three classes of beta-lactamases--A, B and C--have been identified on the basis of their amino-acid sequence; class B beta-lactamases are metalloenzymes, and are clearly distinct from members of class A and C beta-lactamases, which both contain an active-site serine residue involved in the formation of an acyl enzyme with beta-lactam substrates during catalysis. It has been predicted that class C beta-lactamases share common structural features with D,D-carboxypeptidases and class A beta-lactamases, and further, suggested that class A and class C beta-lactamases have the same evolutionary origin as other beta-lactam target enzymes. We report here the refined three-dimensional structure of the class C beta-lactamase from Citrobacter freundii at 2.0-A resolution and confirm the predicted structural similarity. The refined structure of the acyl-enzyme formed with the monobactam inhibitor aztreonam at 2.5-A resolution defines the enzyme's active site and, along with molecular modelling, indicates a mechanism for beta-lactam hydrolysis. This leads to the hypothesis that Tyr 150 functions as a general base during catalysis. |
==About this Structure== | ==About this Structure== | ||
| - | 1FR6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Citrobacter_freundii Citrobacter freundii] with AZR as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] Full crystallographic information is available from [http:// | + | 1FR6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Citrobacter_freundii Citrobacter freundii] with <scene name='pdbligand=AZR:'>AZR</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FR6 OCA]. |
==Reference== | ==Reference== | ||
| Line 14: | Line 14: | ||
[[Category: Citrobacter freundii]] | [[Category: Citrobacter freundii]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Arcy, A | + | [[Category: Arcy, A D.]] |
| - | [[Category: Daly, J | + | [[Category: Daly, J J.]] |
[[Category: Oefner, C.]] | [[Category: Oefner, C.]] | ||
| - | [[Category: Winkler, F | + | [[Category: Winkler, F K.]] |
[[Category: AZR]] | [[Category: AZR]] | ||
[[Category: antibiotic resistance]] | [[Category: antibiotic resistance]] | ||
| Line 24: | Line 24: | ||
[[Category: monobactum]] | [[Category: monobactum]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:41:49 2008'' |
Revision as of 10:41, 21 February 2008
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REFINED CRYSTAL STRUCTURE OF BETA-LACTAMASE FROM CITROBACTER FREUNDII INDICATES A MECHANISM FOR BETA-LACTAM HYDROLYSIS
Overview
Beta-Lactamases (EC 3.5.2.6, 'penicillinases') are a family of enzymes that protect bacteria against the lethal effects of cell-wall synthesis of penicillins, cephalosporins and related antibiotic agents, by hydrolysing the beta-lactam antibiotics to biologically inactive compounds. Their production can, therefore, greatly contribute to the clinical problem of antibiotic resistance. Three classes of beta-lactamases--A, B and C--have been identified on the basis of their amino-acid sequence; class B beta-lactamases are metalloenzymes, and are clearly distinct from members of class A and C beta-lactamases, which both contain an active-site serine residue involved in the formation of an acyl enzyme with beta-lactam substrates during catalysis. It has been predicted that class C beta-lactamases share common structural features with D,D-carboxypeptidases and class A beta-lactamases, and further, suggested that class A and class C beta-lactamases have the same evolutionary origin as other beta-lactam target enzymes. We report here the refined three-dimensional structure of the class C beta-lactamase from Citrobacter freundii at 2.0-A resolution and confirm the predicted structural similarity. The refined structure of the acyl-enzyme formed with the monobactam inhibitor aztreonam at 2.5-A resolution defines the enzyme's active site and, along with molecular modelling, indicates a mechanism for beta-lactam hydrolysis. This leads to the hypothesis that Tyr 150 functions as a general base during catalysis.
About this Structure
1FR6 is a Single protein structure of sequence from Citrobacter freundii with as ligand. Active as Beta-lactamase, with EC number 3.5.2.6 Full crystallographic information is available from OCA.
Reference
Refined crystal structure of beta-lactamase from Citrobacter freundii indicates a mechanism for beta-lactam hydrolysis., Oefner C, D'Arcy A, Daly JJ, Gubernator K, Charnas RL, Heinze I, Hubschwerlen C, Winkler FK, Nature. 1990 Jan 18;343(6255):284-8. PMID:2300174
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