Oefner C


Full name : Oefner Christian

First name : Christian

Mail : Morphochem AG, Basel

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Country : Switzerland

Email : christian.oefner@morphochem.ch

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References (4)

Title : Structural studies of a bifunctional inhibitor of neprilysin and DPP-IV - Oefner_2007_Acta.Crystallogr.D.Biol.Crystallogr_63_975
Author(s) : Oefner C , Pierau S , Schulz H , Dale GE
Ref : Acta Crystallographica D Biol Crystallogr , 63 :975 , 2007
Abstract : Neutral endopeptidase (NEP) is the major enzyme involved in the metabolic inactivation of a number of bioactive peptides including the enkephalins, substance P, endothelin, bradykinin and atrial natriuretic factor, as well as the incretin hormone glucagon-like peptide 1 (GLP-1), which is a potent stimulator of insulin secretion. The activity of GLP-1 is also rapidly abolished by the serine protease dipeptidyl peptidase IV (DPP-IV), which led to an elevated interest in inhibitors of this enzyme for the treatment of type II diabetes. A dual NEP/DPP-IV inhibitor concept is proposed, offering an alternative strategy for the treatment of type 2 diabetes. Here, the synthesis and crystal structures of the soluble extracellular domain of human NEP (residues 52-749) complexed with the NEP, competitive and potent dual NEP/DPP-IV inhibitor MCB3937 are described.
ESTHER : Oefner_2007_Acta.Crystallogr.D.Biol.Crystallogr_63_975
PubMedSearch : Oefner_2007_Acta.Crystallogr.D.Biol.Crystallogr_63_975
PubMedID: 17704566

Title : High-resolution structure of human apo dipeptidyl peptidase IV\/CD26 and its complex with 1-[([2-[(5-iodopyridin-2-yl)amino]-ethyl]amino)-acetyl]-2-cyano-(S)-pyrrolidine - Oefner_2003_Acta.Crystallogr.D.Biol.Crystallogr_59_1206
Author(s) : Oefner C , D'Arcy A , Mac Sweeney A , Pierau S , Gardiner R , Dale GE
Ref : Acta Crystallographica D Biol Crystallogr , 59 :1206 , 2003
Abstract : Dipeptidyl peptidase IV is a multifunctional type II transmembrane serine protease glycoprotein. The high-resolution crystal structure of the homodimeric human apo dipeptidyl peptidase IV has been determined at 1.9 A resolution. In addition, the structure of the binary complex with 1-[([2-[(5-iodopyridin-2-yl)amino]-ethyl]amino)-acetyl]-2-cyano-(S)-pyrrolidine has been solved, revealing the nature of the covalent interaction with the active-site serine.
ESTHER : Oefner_2003_Acta.Crystallogr.D.Biol.Crystallogr_59_1206
PubMedSearch : Oefner_2003_Acta.Crystallogr.D.Biol.Crystallogr_59_1206
PubMedID: 12832764
Gene_locus related to this paper: human-DPP4

Title : Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein - Sussman_1991_Science_253_872
Author(s) : Sussman JL , Harel M , Frolow F , Oefner C , Goldman A , Toker L , Silman I
Ref : Science , 253 :872 , 1991
Abstract : The three-dimensional structure of acetylcholinesterase from Torpedo californica electric organ has been determined by x-ray analysis to 2.8 angstrom resolution. The form crystallized is the glycolipid-anchored homodimer that was purified subsequent to solubilization with a bacterial phosphatidylinositol-specific phospholipase C. The enzyme monomer is an alpha/beta protein that contains 537 amino acids. It consists of a 12-stranded mixed beta sheet surrounded by 14 alpha helices and bears a striking resemblance to several hydrolase structures including dienelactone hydrolase, serine carboxypeptidase-II, three neutral lipases, and haloalkane dehalogenase. The active site is unusual because it contains Glu, not Asp, in the Ser-His-acid catalytic triad and because the relation of the triad to the rest of the protein approximates a mirror image of that seen in the serine proteases. Furthermore, the active site lies near the bottom of a deep and narrow gorge that reaches halfway into the protein. Modeling of acetylcholine binding to the enzyme suggests that the quaternary ammonium ion is bound not to a negatively charged "anionic" site, but rather to some of the 14 aromatic residues that line the gorge.
ESTHER : Sussman_1991_Science_253_872
PubMedSearch : Sussman_1991_Science_253_872
PubMedID: 1678899
Gene_locus related to this paper: torca-ACHE

Title : Structural Studies on Acetylcholinesterase from Torpedo californica -
Author(s) : Sussman JL , Harel M , Frolow F , Oefner C , Toker L , Silman I
Ref : In: Cholinesterases: Structure, Function, Mechanism, Genetics, and Cell Biology , (Massoulie J, Barnard EA, Chatonnet A, Bacou F, Doctor BP, Quinn DM) American Chemical Society, Washington, DC :7 , 1991