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| [[Image:1q15.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_1q15| PDB=1q15 | SCENE= }} | | {{STRUCTURE_1q15| PDB=1q15 | SCENE= }} |
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| '''Carbapenam Synthetase'''
| | ===Carbapenam Synthetase=== |
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| ==Overview==
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| Carbapenam synthetase (CarA) is an ATP/Mg2+-dependent enzyme that catalyzes formation of the beta-lactam ring in (5R)-carbapenem-3-carboxylic acid biosynthesis. CarA is homologous to beta-lactam synthetase (beta-LS), which is involved in clavulanic acid biosynthesis. The catalytic cycles of CarA and beta-LS mediate substrate adenylation followed by beta-lactamization via a tetrahedral intermediate or transition state. Another member of this family of ATP/Mg2+-dependent enzymes, asparagine synthetase (AS-B), catalyzes intermolecular, rather than intramolecular, amide bond formation in asparagine biosynthesis. The crystal structures of apo-CarA and CarA complexed with the substrate (2S,5S)-5-carboxymethylproline (CMPr), ATP analog alpha,beta-methyleneadenosine 5'-triphosphate (AMP-CPP), and a single Mg2+ ion have been determined. CarA forms a tetramer. Each monomer resembles beta-LS and AS-B in overall fold, but key differences are observed. The N-terminal domain lacks the glutaminase active site found in AS-B, and an extended loop region not observed in beta-LS or AS-B is present. Comparison of the C-terminal synthetase active site to that in beta-LS reveals that the ATP binding site is highly conserved. By contrast, variations in the substrate binding pocket reflect the different substrates of the two enzymes. The Mg2+ coordination is also different. Several key residues in the active site are conserved between CarA and beta-LS, supporting proposed roles in beta-lactam formation. These data provide further insight into the structures of this class of enzymes and suggest that CarA might be a versatile target for protein engineering experiments aimed at developing improved production methods and new carbapenem antibiotics.
| | The line below this paragraph, {{ABSTRACT_PUBMED_12890666}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 12890666 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_12890666}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Cma]] | | [[Category: Cma]] |
| [[Category: Cmpr]] | | [[Category: Cmpr]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:44:24 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 03:39:09 2008'' |
