A single amino acid substitution converts cytochrome P45014DM to an inactive form, cytochrome P450SG1: Complete primary structures deduced from cloned DNAs

https://doi.org/10.1016/S0006-291X(88)81087-8Get rights and content

Genes for lanosterol 14-demethylase, cytochrome P45014DM, and a mutated inactive cytochrome P450SG1 were cloned from S. cerevisiae strains D587 and SC1, respectively. A single nucleotide change resulting in substitution of Asp for Gly-310 of cytochrome P45014DM was found to have occured in cytochrome P450SG1. In this protein the 6th ligand to heme iron is a histidine residue instead of a water molecule, which may be the ligand for the active cytochrome P45014DM. Molecular models of the active sites of the cytochrome P45014DM and cytochrome P450SG1 were built by computer modeling on the basis of the known structure of that of cytochrome P450CAM whose crystallographic data are available. The mechanisms which may cause a histidine residue to gain access to the heme iron are discussed.

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