1xny
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(New page: 200px<br /><applet load="1xny" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xny, resolution 2.20Å" /> '''Biotin and propionyl...)
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Revision as of 00:26, 25 November 2007
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Biotin and propionyl-CoA bound to Acyl-CoA Carboxylase Beta Subunit from S. coelicolor (PccB)
Overview
Acetyl-CoA carboxylase (ACC) and propionyl-CoA carboxylase (PCC) catalyze, the carboxylation of acetyl- and propionyl-CoA to generate malonyl- and, methylmalonyl-CoA, respectively. Understanding the substrate specificity, of ACC and PCC will (1) help in the development of novel structure-based, inhibitors that are potential therapeutics against obesity, cancer, and, infectious disease and (2) facilitate bioengineering to provide novel, extender units for polyketide biosynthesis. ACC and PCC in Streptomyces, coelicolor are multisubunit complexes. The core catalytic beta-subunits, PccB and AccB, are 360 kDa homohexamers, catalyzing the transcarboxylation, between biotin and acyl-CoAs. Apo and substrate-bound crystal structures, of PccB hexamers were determined to 2.0-2.8 A. The hexamer assembly forms, a ring-shaped complex. The hydrophobic, highly conserved biotin-binding, pocket was identified for the first time. Biotin and propionyl-CoA bind, perpendicular to each other in the active site, where two oxyanion holes, were identified. N1 of biotin is proposed to be the active site base., Structure-based mutagenesis at a single residue of PccB and AccB allowed, interconversion of the substrate specificity of ACC and PCC. The, di-domain, dimeric interaction is crucial for enzyme catalysis, stability, and substrate specificity; these features are also highly conserved among, biotin-dependent carboxyltransferases. Our findings enable bioengineering, of the acyl-CoA carboxylase (ACCase) substrate specificity to provide, novel extender units for the combinatorial biosynthesis of polyketides.
About this Structure
1XNY is a Single protein structure of sequence from Streptomyces coelicolor with 191 and BTN as ligands. Active as Propionyl-CoA carboxylase, with EC number 6.4.1.3 Full crystallographic information is available from OCA.
Reference
Crystal structure of the beta-subunit of acyl-CoA carboxylase: structure-based engineering of substrate specificity., Diacovich L, Mitchell DL, Pham H, Gago G, Melgar MM, Khosla C, Gramajo H, Tsai SC, Biochemistry. 2004 Nov 9;43(44):14027-36. PMID:15518551
Page seeded by OCA on Sun Nov 25 02:33:37 2007
