title: Crystal structure of a complex between Pseudomonas aeruginosa alkaline protease and its cognate inhibitor: inhibition by a zinc-NH2 coordinative bond.
abstract: Serralysins are a family of metalloproteases secreted by Gram-negative bacteria into the medium in the form of inactive zymogens. Usually, all serralysin secretors have on the same operon a gene coding for a periplasmic 10-kDa protein, which is an inhibitor of the secreted protease. The recent characterization of the inhibitor of the alkaline protease from Pseudomonas aeruginosa revealed a surprisingly low dissociation constant of 4 pm, contrary to earlier studies on homologous systems, where inhibition constants in the microm range were reported. To approach a more accurate understanding, the crystal structure of the complex between inhibitor and protease from P. aeruginosa was determined at 1.74 A resolution and refined to R(free) = 0.204. The structure reported here shows clearly that the N terminus of the inhibitor forms a coordinative bond to the catalytic Zn(2+) ion with a nitrogen-zinc distance of 2.17 A. We conclude that this interaction adds substantially to the complex stability and show also that similar interactions are found in other metzincin-inhibitor complexes.
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, 3012 Bern, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Hege
authors.forename: R E
authors.initials: RE
authors.lastname: Feltzer
authors.forename: R D
authors.initials: RD
authors.lastname: Gray
authors.forename: U
authors.initials: U
authors.lastname: Baumann
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003460:Crystallization; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000737:chemistry*; D011487:Protein Conformation; D015032:Zinc / Q000737:chemistry*
chemical_list: D011480:Protease Inhibitors; D008666:Metalloendopeptidases; C095666:serralysin; D015032:Zinc