Binuclear metallohydrolases: emerging bioremediators and drug targets

Schenk, G., Mitic, N., Gahan, L., Smith, S. and Hadler, K. (2008). Binuclear metallohydrolases: emerging bioremediators and drug targets. In: 9th European Biological Inorganic Chemistry Conference EUROBIC 9. 9th European Biological Inorganic Chemistry Conference, Wroclaw, Poland, (29-38). 2-6 Spetember 2008.


Author Schenk, G.
Mitic, N.
Gahan, L.
Smith, S.
Hadler, K.
Title of paper Binuclear metallohydrolases: emerging bioremediators and drug targets
Conference name 9th European Biological Inorganic Chemistry Conference
Conference location Wroclaw, Poland
Conference dates 2-6 Spetember 2008
Proceedings title 9th European Biological Inorganic Chemistry Conference EUROBIC 9
Place of Publication Italy
Publisher Medimond
Publication Year 2008
Sub-type Fully published paper
ISBN 978-83-60043-10-3
978-88-7587-463-6
Start page 29
End page 38
Total pages 10
Language eng
Abstract/Summary Binuclear metallohydrolases form a large and diverse group of enzymes that are involved in biological functions ranging from bone resorption to signal transduction [1]. Recently, members of this group of enzymes have gained attention due to their ability to degrade (i) most commonly known a-lactam-based antibiotics (and thus contribute strongly to the emergence of drug-resistant pathogens), and (ii) organophosphate (OP) pesticides and nerve agents [2-4]. While the former ability makes these enzymes promising targets for the development of new chemotherapeutics, the latter provides the basis for the development of potent bioremediators. Here, recent advances in the understanding of the structure and function and biotechnological application of two illustrative binuclear metallohydrolases, the purple acid phosphatase (PAP; a target for anti-osteoporotic drugs) and a glycerophosphodiesterase (GpdQ; a promiscuous enzyme with potential as a novel bioremediator) are discussed. For PAP, the combination of spectroscopic, kinetic and structural data led to the proposal of a comprehensive, eight-step catalytic mechanism, whereby the identity of the hydrolysis-initiating nucleophile is dependent on the metal ion composition, the pH and the identity of the substrate [5-7]. GpdQ differs markedly from PAP in several aspects of its molecular mechanism. In the resting state GpdQ is mononuclear and inactive; the addition of a substrate triggers the formation of a catalytically competent binuclear centre. Following hydrolysis and product release the enzyme returns to its mononuclear resting state [7].
Subjects 060107 Enzymes
Q-Index Code EX
Q-Index Status Provisional Code
Additional Notes Abstract number: KL3

 
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Created: Mon, 01 Mar 2010, 11:48:01 EST by Laura McTaggart on behalf of Faculty Of Nat Resources, Agric & Veterinary Sc