Selectivity in a barren landscape: the P450(BioI)-ACP complex.
The cytochromes P450 (P450s) are a superfamily of oxidative haemoproteins that are capable of catalysing a vast range of oxidative transformations, including the oxidation of unactivated alkanes, often with high stereo- and regio-selectivity. Fatty acid hydroxylation by P450s is widespread across both bacteria and higher organisms, with the sites of oxidation and specificity of oxidation varying from system to system. Several key examples are discussed in the present article, with the focus on P450(BioI) (CYP107H1), a biosynthetic P450 found in the biotin operon of Bacillus subtilis. The biosynthetic function of P450(BioI) is the formation of pimelic acid, a biotin precursor, via a multiple-step oxidative cleavage of long-chain fatty acids. P450(BioI) is a member of an important subgroup of P450s that accept their substrates not free in solution, but rather presented by a separate carrier protein. Structural characterization of the P450(BioI)-ACP (acyl-carrier protein) complex has recently been performed, which has revealed the basis for the oxidation of the centre of the fatty acid chain. The P450(BioI)-ACP structure is the first such P450-carrier protein complex to be characterized structurally, with important implications for other biosynthetically intriguing P450-carrier protein complexes.
Cryle
Max J
MJ
Department of Biomolecular Mechanisms, Max-Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany. Max.Cryle@mpimf-heidelberg.mpg.de
D000213:Acyl Carrier Protein / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001412:Bacillus subtilis / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D013379:Substrate Specificity
D000213:Acyl Carrier Protein; D001426:Bacterial Proteins; D005227:Fatty Acids; D046912:Multiprotein Complexes; D003577:Cytochrome P-450 Enzyme System