1jgt
From Proteopedia
(New page: 200px<br /><applet load="1jgt" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jgt, resolution 1.95Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1jgt.gif|left|200px]]<br /><applet load="1jgt" size=" | + | [[Image:1jgt.gif|left|200px]]<br /><applet load="1jgt" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1jgt, resolution 1.95Å" /> | caption="1jgt, resolution 1.95Å" /> | ||
'''CRYSTAL STRUCTURE OF BETA-LACTAM SYNTHETASE'''<br /> | '''CRYSTAL STRUCTURE OF BETA-LACTAM SYNTHETASE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The enzyme beta-lactam synthetase (beta-LS) catalyzes the formation of the | + | The enzyme beta-lactam synthetase (beta-LS) catalyzes the formation of the beta-lactam ring in clavulanic acid, a clinically important beta-lactamase inhibitor. Whereas the penicillin beta-lactam ring is generated by isopenicillin N synthase (IPNS) in the presence of ferrous ion and dioxygen, beta-LS uses ATP and Mg2+ as cofactors. According to sequence alignments, beta-LS is homologous to class B asparagine synthetases (AS-Bs), ATP/Mg2+-dependent enzymes that convert aspartic acid to asparagine. Here we report the first crystal structure of a beta-LS. The 1.95 A resolution structure of Streptomyces clavuligerus beta-LS provides a fully resolved view of the active site in which substrate, closely related ATP analog alpha,beta-methyleneadenosine 5'-triphosphate (AMP-CPP) and a single Mg2+ ion are present. A high degree of substrate preorganization is observed. Comparison to Escherichia coli AS-B reveals the evolutionary changes that have taken place in beta-LS that impede interdomain reaction, which is essential in AS-B, and that accommodate beta-lactam formation. The structural data provide the opportunity to alter the synthetic potential of beta-LS, perhaps leading to the creation of new beta-lactamase inhibitors and beta-lactam antibiotics. |
==About this Structure== | ==About this Structure== | ||
| - | 1JGT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_clavuligerus Streptomyces clavuligerus] with MG, APC, CMA and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1JGT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_clavuligerus Streptomyces clavuligerus] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=APC:'>APC</scene>, <scene name='pdbligand=CMA:'>CMA</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JGT OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Streptomyces clavuligerus]] | [[Category: Streptomyces clavuligerus]] | ||
| - | [[Category: Bachmann, B | + | [[Category: Bachmann, B O.]] |
| - | [[Category: Miller, M | + | [[Category: Miller, M T.]] |
| - | [[Category: Rosenzweig, A | + | [[Category: Rosenzweig, A C.]] |
| - | [[Category: Townsend, C | + | [[Category: Townsend, C A.]] |
[[Category: APC]] | [[Category: APC]] | ||
[[Category: CMA]] | [[Category: CMA]] | ||
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[[Category: clavulanic acid]] | [[Category: clavulanic acid]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:22:26 2008'' |
Revision as of 11:22, 21 February 2008
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CRYSTAL STRUCTURE OF BETA-LACTAM SYNTHETASE
Overview
The enzyme beta-lactam synthetase (beta-LS) catalyzes the formation of the beta-lactam ring in clavulanic acid, a clinically important beta-lactamase inhibitor. Whereas the penicillin beta-lactam ring is generated by isopenicillin N synthase (IPNS) in the presence of ferrous ion and dioxygen, beta-LS uses ATP and Mg2+ as cofactors. According to sequence alignments, beta-LS is homologous to class B asparagine synthetases (AS-Bs), ATP/Mg2+-dependent enzymes that convert aspartic acid to asparagine. Here we report the first crystal structure of a beta-LS. The 1.95 A resolution structure of Streptomyces clavuligerus beta-LS provides a fully resolved view of the active site in which substrate, closely related ATP analog alpha,beta-methyleneadenosine 5'-triphosphate (AMP-CPP) and a single Mg2+ ion are present. A high degree of substrate preorganization is observed. Comparison to Escherichia coli AS-B reveals the evolutionary changes that have taken place in beta-LS that impede interdomain reaction, which is essential in AS-B, and that accommodate beta-lactam formation. The structural data provide the opportunity to alter the synthetic potential of beta-LS, perhaps leading to the creation of new beta-lactamase inhibitors and beta-lactam antibiotics.
About this Structure
1JGT is a Single protein structure of sequence from Streptomyces clavuligerus with , , and as ligands. Full crystallographic information is available from OCA.
Reference
Structure of beta-lactam synthetase reveals how to synthesize antibiotics instead of asparagine., Miller MT, Bachmann BO, Townsend CA, Rosenzweig AC, Nat Struct Biol. 2001 Aug;8(8):684-9. PMID:11473258
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