Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glyoxalase II enzymes catalyze the hydrolysis of a thioester substrate and have been found to coordinate a variety of dimetal combinations, including Fe(III)Zn(II), within the enzyme active site. Of relevance to these enzymes, the thioester hydrolysis reactivity of the Fe(III)Zn(II) compound [(BPBPMP)Fe(III)Zn(II)(mu-OAc)(2)]ClO(4) (1) was evaluated in CH(3)CN/H(2)O (50:50; buffered) at 26.5 degrees C. Thioester hydrolysis in the absence and presence of 1 was monitored using (2)H NMR by following the loss of the thioester -SCD(3) signal. Two products are generated in the reaction involving the metal complex, D(3)CSSCD(3) and CD(3)SH. Kinetic studies of this reaction as a function of pH revealed maximum rate above the pK(a) of a Zn-OH(2) moiety of [(BPBPMP)Fe(III)(OH)(mu-OH)Zn(II)(OH(2))](+), which forms from 1 in CH(3)CN/H(2)O (50:50). UV-vis and electron paramagnetic resonance (EPR) studies of a single turnover thioester hydrolysis reaction in the presence of 1 equiv of 1 at pH = 9.0 suggest that the thioester does not initially interact with the Fe(III) center, but that changes occur at this site over the course of the reaction. The formation of a Fe(III)-SCD(3) moiety is proposed based on the observed D(3)CSSCD(3) formation, which likely results from redox activity involving a iron(III) thiolate species. A mechanism for thioester hydrolysis is proposed involving initial coordination of the deprotonated alpha-hydroxy thioester to the zinc center followed by nucleophilic attack by a terminal Fe(III)-OH moiety and thiolate leaving group stabilization by the Fe(III) center. Overall, this study outlines a novel approach of using an aliphatic thioester substrate and (2)H NMR to provide mechanistic insight into thioester hydrolysis involving an Fe(III)Zn(II) complex of relevance to glyoxalase II.
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PMID:Thioester hydrolysis reactivity of an Fe(III)Zn(II) complex. 1982 73

The mononuclear zinc complex [(bpta)Zn](ClO(4))(2).0.5H(2)O promotes the hydrolysis of the thioester PhCH(OH)C(O)SCD(3) when dissolved in CH(3)CN:H(2)O (50:50 buffered at pH 9.0). This reaction results in the formation of a mixture of CD(3)SH and a zinc thiolate complex, the latter of which can be protonated to generate additional CD(3)SH. Kinetic studies revealed an overall second-order reaction with an activation energy that is similar to that found for aqueous OH(-) promoted thioester hydrolysis. These studies represent the first investigation of chemistry relevant to that occurring in the monozinc-containing form of human glyoxalase II.
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PMID:Thioester hydrolysis promoted by a mononuclear zinc complex. 2003 13