title: Structure of recombinant human renin, a target for cardiovascular-active drugs, at 2.5 A resolution.
abstract: The x-ray crystal structure of recombinant human renin has been determined. Molecular dynamics techniques that included crystallographic data as a restraint were used to improve an initial model based on porcine pepsinogen. The present agreement factor for data from 8.0 to 2.5 angstroms (A) is 0.236. Some of the surface loops are poorly determined, and these disordered regions border a 30 A wide solvent channel. Comparison of renin with other aspartyl proteinases shows that, although the structural cores and active sites are highly conserved, surface residues, some of which are critical for specificity, vary greatly (up to 10A). Knowledge of the actual structure, as opposed to the use of models based on related enzymes, should facilitate the design of renin inhibitors.
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Canada.
authors.forename: A R
authors.initials: AR
authors.lastname: Sielecki
authors.forename: K
authors.initials: K
authors.lastname: Hayakawa
authors.forename: M
authors.initials: M
authors.lastname: Fujinaga
authors.forename: M E
authors.initials: ME
authors.lastname: Murphy
authors.forename: M
authors.initials: M
authors.lastname: Fraser
authors.forename: A K
authors.initials: AK
authors.lastname: Muir
authors.forename: C T
authors.initials: CT
authors.lastname: Carilli
authors.forename: J A
authors.initials: JA
authors.lastname: Lewicki
authors.forename: J D
authors.initials: JD
authors.lastname: Baxter
authors.forename: M N
authors.initials: MN
authors.lastname: James
mesh_terms: D016282:Aspartic Acid Endopeptidases; D002317:Cardiovascular Agents / Q000494:pharmacology; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D010434:Pepsin A / Q000378:metabolism; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000378:metabolism; D012083:Renin / Q000378:metabolism
chemical_list: D002317:Cardiovascular Agents; D011994:Recombinant Proteins; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; D010434:Pepsin A; D012083:Renin