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| - | [[Image:2a81.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_2a81| PDB=2a81 | SCENE= }} | | {{STRUCTURE_2a81| PDB=2a81 | SCENE= }} |
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| - | '''carboxymethylproline synthase (CarB) from pectobacterium carotovora, complexed with acetyl CoA and bicine'''
| + | ===carboxymethylproline synthase (CarB) from pectobacterium carotovora, complexed with acetyl CoA and bicine=== |
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| - | ==Overview==
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| - | The first step in the biosynthesis of the medicinally important carbapenem family of beta-lactam antibiotics is catalyzed by carboxymethylproline synthase (CarB), a unique member of the crotonase superfamily. CarB catalyzes formation of (2S,5S)-carboxymethylproline [(2S,5S)-t-CMP] from malonyl-CoA and l-glutamate semialdehyde. In addition to using a cosubstrate, CarB catalyzes C-C and C-N bond formation processes as well as an acyl-coenzyme A hydrolysis reaction. We describe the crystal structure of CarB in the presence and absence of acetyl-CoA at 2.24 A and 3.15 A resolution, respectively. The structures reveal that CarB contains a conserved oxy-anion hole probably required for decarboxylation of malonyl-CoA and stabilization of the resultant enolate. Comparison of the structures reveals that conformational changes (involving His(229)) in the cavity predicted to bind l-glutamate semialdehyde occur on (co)substrate binding. Mechanisms for the formation of the carboxymethylproline ring are discussed in the light of the structures and the accompanying studies using isotopically labeled substrates; cyclization via 1,4-addition is consistent with the observed labeling results (providing that hydrogen exchange at the C-6 position of carboxymethylproline does not occur). The side chain of Glu(131) appears to be positioned to be involved in hydrolysis of the carboxymethylproline-CoA ester intermediate. Labeling experiments ruled out the possibility that hydrolysis proceeds via an anhydride in which water attacks a carbonyl derived from Glu(131), as proposed for 3-hydroxyisobutyryl-CoA hydrolase. The structural work will aid in mutagenesis studies directed at altering the selectivity of CarB to provide intermediates for the production of clinically useful carbapenems. | + | The line below this paragraph, {{ABSTRACT_PUBMED_16096274}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 16096274 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_16096274}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Carbapenem]] | | [[Category: Carbapenem]] |
| | [[Category: Crotonase]] | | [[Category: Crotonase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 18:43:35 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 06:34:15 2008'' |
Revision as of 03:34, 28 July 2008
Template:STRUCTURE 2a81
carboxymethylproline synthase (CarB) from pectobacterium carotovora, complexed with acetyl CoA and bicine
Template:ABSTRACT PUBMED 16096274
About this Structure
2A81 is a Single protein structure of sequence from Pectobacterium carotovorum. Full crystallographic information is available from OCA.
Reference
Structural and mechanistic studies on carboxymethylproline synthase (CarB), a unique member of the crotonase superfamily catalyzing the first step in carbapenem biosynthesis., Sleeman MC, Sorensen JL, Batchelar ET, McDonough MA, Schofield CJ, J Biol Chem. 2005 Oct 14;280(41):34956-65. Epub 2005 Aug 11. PMID:16096274
Page seeded by OCA on Mon Jul 28 06:34:15 2008
