title: Nitro as a novel zinc-binding group in the inhibition of carboxypeptidase A.
abstract: 2-Substituted 3-nitropropanoic acids were designed and synthesized as inhibitors against carboxypeptidase A (CPA). (R)-2-Benzyl- 3-nitropropanoic acid showed a potent inhibition against CPA (K(i)=0.15 microM). X-ray crystallography discloses that the nitro group well mimics the transition state occurred in the hydrolysis catalyzed by CPA, that is, an O,O'-bidentate coordination to the zinc ion and the two respective hydrogen bonds with Glu-270 and Arg-127. Because the nitro group is a planar species, we proposed (R)-2-benzyl-3-nitropropanoic acid as a pseudo-transition-state analog inhibitor against CPA.
authors.affiliation: Department of Chemistry, Yanbian University, Yanji, Jilin 133002, China.
authors.forename: Si-Hong
authors.initials: SH
authors.lastname: Wang
authors.forename: Shou-Feng
authors.initials: SF
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Xuan
authors.forename: Zong-Hao
authors.initials: ZH
authors.lastname: Zeng
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Jin
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.forename: Guan Rong
authors.initials: GR
authors.lastname: Tian
mesh_terms: D043422:Carboxypeptidases A / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D002384:Catalysis; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry*; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D043422:Carboxypeptidases A; D015032:Zinc; D009584:Nitrogen