2a7k

Structural highlights

Function

CARB_PECCC Catalyzes the formation of (2S,5S)-carboxymethylproline (t-CMP) from malonyl-CoA and (S)-1-pyrroline-5-carboxylate, the first step in the biosynthesis of (5R)-carbapen-2-em-3-carboxylate, a beta-lactam antibiotic of the carbapenem class (PubMed:15595850, PubMed:14625287). Also catalyzes the independent decarboxylation of malonyl-CoA and methylmalonyl-CoA and the hydrolysis of CoA esters such as acetyl-CoA and propionyl-CoA (PubMed:15595850). Catalyzes the reaction with a C2 epimeric mixture of methylmalonyl-CoA to give a 55:45 mixture of (6R)- and (6S)-epimers of 6-methyl-t-CMP, under standard incubation conditions (PubMed:21505494).^{[1] [2] [3] [4] [5]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Sleeman MC, Schofield CJ. Carboxymethylproline synthase (CarB), an unusual carbon-carbon bond-forming enzyme of the crotonase superfamily involved in carbapenem biosynthesis. J Biol Chem. 2004 Feb 20;279(8):6730-6. Epub 2003 Nov 18. PMID:14625287 doi:http://dx.doi.org/10.1074/jbc.M311824200
2. ↑ Gerratana B, Arnett SO, Stapon A, Townsend CA. Carboxymethylproline synthase from Pectobacterium carotorova: a multifaceted member of the crotonase superfamily. Biochemistry. 2004 Dec 21;43(50):15936-45. PMID:15595850 doi:http://dx.doi.org/10.1021/bi0483662
3. ↑ Sorensen JL, Sleeman MC, Schofield CJ. Synthesis of deuterium labelled L- and D-glutamate semialdehydes and their evaluation as substrates for carboxymethylproline synthase (CarB)--implications for carbapenem biosynthesis. Chem Commun (Camb). 2005 Mar 7;(9):1155-7. Epub 2005 Jan 13. PMID:15726176 doi:http://dx.doi.org/10.1039/b416423g
4. ↑ Batchelar ET, Hamed RB, Ducho C, Claridge TD, Edelmann MJ, Kessler B, Schofield CJ. Thioester hydrolysis and C-C bond formation by carboxymethylproline synthase from the crotonase superfamily. Angew Chem Int Ed Engl. 2008;47(48):9322-5. doi: 10.1002/anie.200803906. PMID:18972478 doi:http://dx.doi.org/10.1002/anie.200803906
5. ↑ Hamed RB, Gomez-Castellanos JR, Thalhammer A, Harding D, Ducho C, Claridge TD, Schofield CJ. Stereoselective C-C bond formation catalysed by engineered carboxymethylproline synthases. Nat Chem. 2011 May;3(5):365-71. doi: 10.1038/nchem.1011. Epub 2011 Apr 3. PMID:21505494 doi:http://dx.doi.org/10.1038/nchem.1011