Learn More
beta-ketoacyl (acyl carrier protein) reductase (beta-k-ACPR) enzymes are essential to fatty acid synthesis in bacteria. The analyses revealed the most primitive member of the beta-k-ACPRs family was a NADP reductase where NADP was recognised by a Thr residue in the beta2alpha3 turn. Aromatic residue stacking at the dimer interface and a previously(More)
Separate genes encode the human type 1 (placenta, breast tumors, other peripheral tissues) and type 2 (gonad, adrenal) isoforms of 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD1, 3 beta-HSD2). Mutagenesis of 3 beta-HSD1 produced the Y154F, H156Y and K158Q mutant enzymes in the probable Y(154)-P-H(156)-S-K(158) catalytic motif. The H(156)Y mutant(More)
The human type 1 (placenta, breast tumors) and type 2 (gonads, adrenals) isoforms of 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD) are key enzymes in steroidogenic pathways leading to the production of all active steroid hormones. Kinetic analyses of purified 3beta-HSD1 show that the Michaelis-Menten constants (Km) for substrates and cofactor are(More)
The crystal structure of the nonstoichiometric complex of gramicidin D with NaI has been studied using synchrotron radiation at 100 K. The limiting resolution was 1.25 A and the R factor was 16% for 19 883 observed reflections. The general architecture of the antiparallel two-stranded gramicidin dimers in the studied crystal was a right-handed antiparallel(More)
Short-chain dehydrogenase reductase (SDR) enzymes influence mammalian reproduction, hypertension, neoplasia, and digestion. The three-dimensional structures of two members of the SDR family reveal the position of the conserved catalytic triad, a possible mechanism of keto-hydroxyl interconversion, the molecular mechanism of inhibition, and the basis for(More)
The inactive methadone analog threo-5-methylmethadone has a solid-state conformation in which the nitrogen is antiperiplanar to the tertiary carbon C(4). Since threo-5-methylmethadone exhibits no opioid agonism either in vivo or in vitro, methadone analogs probably do not have this conformation when bound to an opioid receptor. The potent agonist(More)
Search vectors composed of Gly, Ala, Arg, and Pro (GARP) residues retrieve 98% of each of the ribosomal proteins in prokaryotic species with no false hits. Different combinations of G, A, R and P and insertions differentiate each ribosomal protein from all others. Amino acids in two sequence positions separate Gram+ from Gram- bacteria. Specific residues(More)
Mammalian 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD) is a member of the short chain dehydrogenase/reductase. It is a key steroidogenic enzyme that catalyzes the first step of the multienzyme pathway conversion of circulating dehydroepiandrosterone and pregnenolone to active steroid hormones. A three dimensional model of a ternary complex of(More)
Significant sequence homology has been detected between prokaryotic beta-ketoacyl-[acyl carrier protein] reductases (BKR) and eukaryotic 17beta-hydroxysteroid dehydrogenases type 8 (17beta-HSD_8). Three-dimensional models of ternary complexes of human 17beta-HSD_8 with NAD cofactor and two chemically distinct substrates, the BKR substrate(More)
20 beta-Hydroxysteroid dehydrogenase from the cytosolic fraction of neonatal pig testis is a NADPH-dependent enzyme that catalyzes the reduction of the C-20 ketone of C21-steroids. It is 85% homologous in amino acid sequence to the human enzyme, carbonyl reductase. The enzyme has been crystallized from 36% saturated ammonium sulfate in 10 mM(More)