Metalloantibodies: mercury(II)-dependent acyl transferases.
A new approach for the elicitation of metal-dependent catalytic antibodies for ester hydrolysis is described. A coordinatively unsaturated mercury complex 1-(Hg), has been utilized as a hapten to elicit antibodies that incorporate mercury(II) as a Lewis acid cofactor. From a panel of monoclonal antibodies generated to 1-(Hg), antibody 38G2 was found to hydrolyze the ester 3 in the presence of HgCl(2) [K(m)app(3)=345 microM; K(m)app(Hg(2+))=87 microM; k(cat)app/k(uncat)=3 x 10(2)]. This is the first example of a biocatalyst that enlists mercuric ion as a cofactor and it is anticipated that this approach will open new avenues for exploitation of metals thought previously beyond the scope of protein catalysts.
Brümmer
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Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Hoffman
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TZ
Janda
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D000217:Acyltransferases / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D017151:Antibodies, Catalytic / Q000737:chemistry* / Q000187:drug effects / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000187:drug effects / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006241:Haptens / Q000737:chemistry / Q000276:immunology; D006868:Hydrolysis / Q000187:drug effects; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008628:Mercury / Q000276:immunology; D008670:Metals / Q000276:immunology*; D008958:Models, Molecular; D010710:Phosphates / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology
D017151:Antibodies, Catalytic; D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D006241:Haptens; D008670:Metals; D010710:Phosphates; C083120:phosphorodithioic acid; D000217:Acyltransferases; D008628:Mercury