Induced fit and the catalytic mechanism of isocitrate dehydrogenase.
Induced fit and the catalytic mechanism of isocitrate dehydrogenase.
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DOI：
10.1021/bi300483w
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发表时间：
2012-09-11
期刊：
影响因子：
2.9
通讯作者：
Matias PM
中科院分区：
文献类型：
--
作者：
Gonçalves S;Miller SP;Carrondo MA;Dean AM;Matias PM
NADP+ dependent isocitrate dehydrogenase (IDH; EC 1.1.1.42) belongs to a large family of α-hydroxyacid oxidative β-decarboxylases that catalyze similar three-step reactions, with dehydrogenation to an oxaloacid intermediate preceding β-decarboxylation to an enol intermediate followed by tautomerization to the final α-ketone product. A comprehensive view of the induced fit needed for catalysis is revealed on comparing the first “fully closed” crystal structures of a pseudo-Michaelis complex of wild-type Escherichia coli IDH (EcoIDH) and the “fully closed” reaction product complex of the K100M mutant with previously obtained “quasi-closed” and “open” conformations. Conserved catalytic residues, binding the nicotinamide ring of NADP+ and the metal-bound substrate, move as rigid bodies during domain closure by a hinge motion that spans the central β-sheet in each monomer. Interactions established between Thr105 and Ser113, which flank the “phosphorylation loop”, and the nicotinamide mononucleotide moiety of NADP+ establish productive coenzyme binding. Electrostatic interactions of a Lys100-Leu103-Asn115-Glu336 tetrad play a pivotal role in assembling a catalytically competent active site. As predicted, Lys230* is positioned to deprotonate/reprotonate the α-hydroxyl in both reaction steps and Tyr160 moves into position to protonate C3 following β-decarboxylation. A proton relay from the catalytic triad Tyr160-Asp307-Lys230* connects the α-hydroxyl of isocitrate to the bulk solvent to complete the picture of the catalytic mechanism.
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影响因子：
64.8
作者：
通讯作者：
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影响因子：
4.8
作者：
Ceccarelli, C;Grodsky, NB;Bahnson, BJ
通讯作者：
Bahnson, BJ
影响因子：
2.9
作者：
FinerMoore, J;Tsutakawa, SE;Stroud, RM
通讯作者：
Stroud, RM
影响因子：
2.9
作者：
Doyle, SA;Beernink, PT;Koshland, DE
通讯作者：
Koshland, DE
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH