Biomaterial Database

Cooperative catalysis in the homodimer subunits of xanthine oxidase. 2004

Lin Ai Tai, and Kuo Chu Hwang

Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan.

Xanthine oxidase (XOD) consists of two identical subunits. For the past 50 years or so, it was assumed that the two subunits carry out catalysis independently. Herein, we report that the presence of 6-formylpterin (6FP) or other substrates (such as xanthine or xanthopterin) at one of the two active sites affects the binding affinity and catalysis rate of 6FP at the other. When the two XOD active sites were occupied by two 6FPs simultaneously, the conversion rate (2.8 x 10(-3) s(-1)) of 6FP to 6CP is 2.95-fold faster than the conversion rate (0.95 x 10(-3) s(-1)) in the case of single 6FP bound condition. The presence of xanthine can accelerate the catalysis rate of 6FP by XOD as well as the activity-recovering rate of alloxanthine-inhibited XOD. Our experimental observations demonstrate unambiguously that the two XOD subunits are strongly cooperative in both binding and catalysis. The inhibition constant (Ki) of 6FP toward XOD was measured by a stopped-flow method to be 0.94 nM.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008956	Models, Chemical	Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.	Chemical Models,Chemical Model,Model, Chemical
D011622	Pterins	Compounds based on 2-amino-4-hydroxypteridine.	Pterin
D002384	Catalysis	The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.	Catalyses
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D013053	Spectrophotometry	The art or process of comparing photometrically the relative intensities of the light in different parts of the spectrum.
D013379	Substrate Specificity	A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.	Specificities, Substrate,Specificity, Substrate,Substrate Specificities
D014969	Xanthine Oxidase	An iron-molybdenum flavoprotein containing FLAVIN-ADENINE DINUCLEOTIDE that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria.	Hypoxanthine Oxidase,Hypoxanthine Dehydrogenase,Hypoxanthine-Xanthine Oxidase,Purine-Xanthine Oxidase,Dehydrogenase, Hypoxanthine,Hypoxanthine Xanthine Oxidase,Oxidase, Hypoxanthine,Oxidase, Hypoxanthine-Xanthine,Oxidase, Purine-Xanthine,Oxidase, Xanthine,Purine Xanthine Oxidase
D019281	Dimerization	The process by which two molecules of the same chemical composition form a condensation product or polymer.	Dimerizations