ORBi: Charlier Paulette - Active-site-directed inactivators of the Zn2+-containing D-alanyl-D-alanine-cleaving carboxypeptidase of Streptomyces albus G.

Reference : Active-site-directed inactivators of the Zn2+-containing D-alanyl-D-alanine-cleaving car...


	Document type :	Scientific journals : Article
	Discipline(s) :	Physical, chemical, mathematical & earth Sciences : Chemistry Human health sciences : Pharmacy, pharmacology & toxicology Life sciences : Biochemistry, biophysics & molecular biology
	To cite this reference:	http://hdl.handle.net/2268/78089

Title :	Active-site-directed inactivators of the Zn2+-containing D-alanyl-D-alanine-cleaving carboxypeptidase of Streptomyces albus G.
Language :	English
Author, co-author :	Charlier, Paulette [Université de Liège - ULg > Faculté de Médecine, Institut de Chimie > Service de Microbiologie > >]
	Dideberg, Otto [Université de Liège - ULg > Faculté des Sciences, Institut de Physique > Service de Cristallographie > > >]
	Jamoulle, Jean-Claude [Université de Liège - ULg > Faculté des Médecine, Institut de Pharmacie > Service de Chimie Analytique > >]
	Frère, Jean-Marie [Université de Liège - ULg > Faculté de Médecine, Institut de Chimie > Service de Microbiologie > >]
	Ghuysen, Jean-Marie [Université de Liège - ULg > Faculté de Médecine, Institut de Chimie > Service de Microbiologie > > >]
	Dive, Georges [Université de Liège - ULg > Faculté des Médecine, Institut de Pharmacie > Service de Chimie Analytique > >]
	Lamotte, Josette [Université de Liège - ULg > Faculté des Sciences, Institut de Physique > Service de Cristallographie > >]
Publication date :	1984
Journal title :	Biochemical Journal
Publisher :	Portland Press
Volume :	219
Issue/season :	3
Pages :	763-772
Audience :	International
ISSN :	0264-6021
e-ISSN :	1470-8728
City :	London
Country :	United Kingdom
Keywords :	[en] Binding Sites/drug effects ; Carboxypeptidases/antagonists & inhibitors ; Gold/pharmacology ; Iridium/pharmacology ; Metals/pharmacology ; Models, Molecular ; Platinum/pharmacology ; Streptomyces/enzymology ; Uranium/pharmacology ; X-Ray Diffraction
Abstract :	[en] Several types of active-site-directed inactivators (inhibitors) of the Zn2+-containing D-alanyl-D-alanine-cleaving carboxypeptidase were tested. (i) Among the heavy-atom-containing compounds examined, K2Pt(C2O4)2 inactivates the enzyme with a second-order rate constant of about 6 X 10(-2)M-1 X S-1 and has only one binding site located close to the Zn2+ cofactor within the enzyme active site. (ii) Several compounds possessing both a C-terminal carboxylate function and, at the other end of the molecule, a thiol, hydroxamate or carboxylate function were also examined. 3-Mercaptopropionate (racemic) and 3-mercaptoisobutyrate (L-isomer) inhibit the enzyme competitively with a Ki value of 5 X 10 X 10(-9)M. (iii) Classical beta-lactam compounds have a very weak inhibitory potency. Depending on the structure of the compounds, enzyme inhibition may be competitive (and binding occurs to the active site) or non-competitive (and binding causes disruption of the protein crystal lattice). (iv) 6-beta-Iodopenicillanate inactivates the enzyme in a complex way. At high beta-lactam concentrations, the pseudo-first-order rate constant of enzyme inactivation has a limit value of 7 X 10(-4)S-1 X 6-beta-Iodopenicillanate binds to the active site just in front of the Zn2+ cofactor and superimposes histidine-190, suggesting that permanent enzyme inactivation is by reaction with this latter residue.
Target :	Researchers ; Professionals
Permalink :	http://hdl.handle.net/2268/78089
	also: http://hdl.handle.net/2268/97423

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