Albany 2001

category image Biomolecular
SUNY at Albany
June 19-23, 2001

Structural genomics of cholesterol biosynthesis: mevalonate 5-diphosphate decarboxylase and isopentenyl diphosphate isomerase

X-ray structures of mevalonate 5-diphosphate decarboxylase (MDD, E.C. and isopentenyl disphosphate isomerase (IDI, E.C. have been determined at 2.3? and 2.5?, respectively. Structural similarity searches and comparative protein structure modeling with these two essential cholesterol biosynthesis enzymes revealed unexpected structural relationships. MDD is a two-domain, alpha/beta ATP-dependent enzyme with a recognizable P loop nucleotide-binding site. MDD shares the same fold as the GHMP kinase superfamily, which includes galactokinases (GK, E.C., homoserine kinases (HSK, E.C., mevalonate kinases (MK, E.C., phosphomevalonate kinase (PMK, E.C., isopentenyl phosphate kinases (IPK, E.C. 2.7.1.-), and a related group of eleven prokaryotic hypothetical proteins. MK, PMK, and IPK are all involved in sterol biosynthesis. IDI is a single domain, alpha/beta metallo-enzyme that proved to be part of an enzyme superfamily that includes the NPPX family of nucleotide diphosphate X group hydrolases, diphospho-inositol hydrolases, and thaimine PP kinases.

Jeffrey B. Bonanno(3,2,), Carme Edo(3), Narayanan Eswar(3), Ursula Pieper(3), Michael J. Romanowski(3), Sue Ellen Gerchman(1), Helen Kycia(1), F. William Studier(1), Andrej Sali(3), and Stephen K. Burley(3,2,*)

Department of Biology(1), Brookhaven National Laboratory Howard Hughes Medical Institute(2), Laboratories of Molecular Biophysics(3), The Rockefeller University, 1230 York Avenue, New York, NY 10021
Ph: (212) 327-8856; fx: (212) 327-8337; burley@rockefeller.edu