Linked Life Data

11880619

Source:http://linkedlifedata.com/resource/pubmed/id/11880619

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2002-3-7
pubmed:abstractText
A strategy for the preparation of semisynthetic copper(II)-based catalytic metalloproteins is described in which a metal-binding bis-imidazole cofactor is incorporated into the combining site of the aldolase antibody 38C2. Antibody 38C2 features a large hydrophobic-combining site pocket with a highly nucleophilic lysine residue, Lys(H93), that can be covalently modified. A comparison of several lactone and anhydride reagents shows that the latter are the most effective and general derivatizing agents for the 38C2 Lys residue. A bis-imidazole anhydride (5) was efficiently prepared from N-methyl imidazole. The 38C2-5-Cu conjugate was prepared by either (i) initial derivatization of 38C2 with 5 followed by metallation with CuCl2, or (ii) precoordination of 5 with CuCl2 followed by conjugation with 38C2. The resulting 38C2-5-Cu conjugate was an active catalyst for the hydrolysis of the coordinating picolinate ester 11, following Michaelis-Menten kinetics [kcat(11) = 2.3 min(-1) and Km(11) 2.2 mM] with a rate enhancement [kcat(11)k(uncat)(11)] of 2.1 x 10(5). Comparison of the second-order rate constants of the modified 38C2 and the Cu(II)-bis-imidazolyl complex k(6-CuCl2) gives a rate enhancement of 3.5 x 10(4) in favor of the antibody complex with an effective molarity of 76.7 M, revealing a significant catalytic benefit to the binding of the bis-imidazolyl ligand into 38C2.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/11880619-10214700, http://linkedlifedata.com/resource/pubmed/commentcorrection/11880619-11028916, http://linkedlifedata.com/resource/pubmed/commentcorrection/11880619-11553463, http://linkedlifedata.com/resource/pubmed/commentcorrection/11880619-1775514, http://linkedlifedata.com/resource/pubmed/commentcorrection/11880619-2116666, http://linkedlifedata.com/resource/pubmed/commentcorrection/11880619-2395868, http://linkedlifedata.com/resource/pubmed/commentcorrection/11880619-2847779, http://linkedlifedata.com/resource/pubmed/commentcorrection/11880619-2922606, http://linkedlifedata.com/resource/pubmed/commentcorrection/11880619-5015675, http://linkedlifedata.com/resource/pubmed/commentcorrection/11880619-5845280, http://linkedlifedata.com/resource/pubmed/commentcorrection/11880619-7893699, http://linkedlifedata.com/resource/pubmed/commentcorrection/11880619-8341642, http://linkedlifedata.com/resource/pubmed/commentcorrection/11880619-8433968, http://linkedlifedata.com/resource/pubmed/commentcorrection/11880619-8525368, http://linkedlifedata.com/resource/pubmed/commentcorrection/11880619-9342312, http://linkedlifedata.com/resource/pubmed/commentcorrection/11880619-9405338
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0027-8424
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
99
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2648-53
pubmed:dateRevised
2010-9-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
A cofactor approach to copper-dependent catalytic antibodies.
pubmed:affiliation
Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019, USA. kmnicholas@chemdept.chem.ou.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't