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Protostadienol synthase from Aspergillus fumigatus: functional conversion into lanosterol synthase.

Abstract：

:Oxidosqualene:protostadienol cyclase (OSPC) from the fungus Aspergillus fumigatus, catalyzes the cyclization of (3S)-2,3-oxidosqualene into protosta-17(20)Z,24-dien-3beta-ol which is the precursor of the steroidal antibiotic helvolic acid. To shed light on the structure-function relationship between OSPC and oxidosqualene:lanosterol cyclase (OSLC), we constructed an OSPC mutant in which the C-terminal residues (702)APPGGMR(708) were replaced with (702)NKSCAIS(708), as in human OSLC. As a result, the mutant no longer produced the protostadienol, but instead efficiently produced a 1:1 mixture of lanosterol and parkeol. This is the first report of the functional conversion of OSPC into OSLC, which resulted in a 14-fold decrease in the V(max)/K(M) value, whereas the binding affinity for the substrate did not change significantly. Homology modeling suggested that stabilization of the C-20 protosteryl cation by the active-site Phe701 through cation-pi interactions is important for the product outcome between protostadienol and lanosterol.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Kimura M,Kushiro T,Shibuya M,Ebizuka Y,Abe I

doi

10.1016/j.bbrc.2009.11.160

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

899-902

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(09)02356-0

journal_volume

391

pub_type

杂志文章

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