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Catalytic mechanism of quinoprotein methanol dehydrogenase: A theoretical and x-ray crystallographic investigation.

ABSTRACT: The catalytic mechanism of the reductive half reaction of the quinoprotein methanol dehydrogenase (MDH) is believed to proceed either through a hemiketal intermediate or by direct transfer of a hydride ion from the substrate methyl group to the cofactor, pyrroloquinoline quinone (PQQ). A crystal structure of the enzyme-substrate complex of a similar quinoprotein, glucose dehydrogenase, has recently been reported that strongly favors the hydride transfer mechanism in that enzyme. A theoretical analysis and an improved refinement of the 1.9-A resolution crystal structure of MDH from Methylophilus methylotrophus W3A1 in the presence of methanol, reported earlier, indicates that the observed tetrahedral configuration of the C-5 atom of PQQ in that study represents the C-5-reduced form of the cofactor and lends support for a hydride transfer mechanism for MDH.

SUBMITTER: Zheng YJ

PROVIDER: S-EPMC14603 | biostudies-literature | 2001 Jan

REPOSITORIES: biostudies-literature

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Catalytic mechanism of quinoprotein methanol dehydrogenase: A theoretical and x-ray crystallographic investigation.

Zheng Y J YJ Xia Zx Chen Zw Mathews F S FS Bruice T C TC

Proceedings of the National Academy of Sciences of the United States of America 20010109 2

The catalytic mechanism of the reductive half reaction of the quinoprotein methanol dehydrogenase (MDH) is believed to proceed either through a hemiketal intermediate or by direct transfer of a hydride ion from the substrate methyl group to the cofactor, pyrroloquinoline quinone (PQQ). A crystal structure of the enzyme-substrate complex of a similar quinoprotein, glucose dehydrogenase, has recently been reported that strongly favors the hydride transfer mechanism in that enzyme. A theoretical an ...[more]

PMID: 11149955

Similar Datasets

Mechanism of methanol oxidation by quinoprotein methanol dehydrogenase.

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| S-EPMC3020142 | biostudies-literature

Mechanisms of ammonia activation and ammonium ion inhibition of quinoprotein methanol dehydrogenase: a computational approach.

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| S-EPMC3080164 | biostudies-literature

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| S-EPMC3686309 | biostudies-literature

Structure and mechanism of soluble quinoprotein glucose dehydrogenase.

Project description:Soluble glucose dehydrogenase (s-GDH; EC 1.1.99.17) is a classical quinoprotein which requires the cofactor pyrroloquinoline quinone (PQQ) to oxidize glucose to gluconolactone. The reaction mechanism of PQQ-dependent enzymes has remained controversial due to the absence of comprehensive structural data. We have determined the X-ray structure of s-GDH with the cofactor at 2.2 A resolution, and of a complex with reduced PQQ and glucose at 1.9 A resolution. These structures reveal the active site of s-GDH, and show for the first time how a functionally bound substrate interacts with the cofactor in a PQQ-dependent enzyme. Twenty years after the discovery of PQQ, our results finally provide conclusive evidence for a reaction mechanism comprising general base-catalyzed hydride transfer, rather than the generally accepted covalent addition-elimination mechanism. Thus, PQQ-dependent enzymes use a mechanism similar to that of nicotinamide- and flavin-dependent oxidoreductases.

| S-EPMC1171589 | biostudies-other

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| S-EPMC2334996 | biostudies-literature

Mechanism of reaction of allylamine with the quinoprotein methylamine dehydrogenase.

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| S-EPMC1136951 | biostudies-other

Characterization of mutant forms of the quinoprotein methanol dehydrogenase lacking an essential calcium ion.

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| S-EPMC1133066 | biostudies-other

Crystallization and preliminary X-ray crystallographic analysis of rabbit L-gulonate 3-dehydrogenase.

Project description:Rabbit L-gulonate 3-dehydrogenase was crystallized using the oil-microbatch method at 295 K. X-ray diffraction data were collected to 1.70 A resolution from a crystal at 100 K using synchrotron radiation. The crystal belongs to the C-centred monoclinic space group C2, with unit-cell parameters a = 71.81, b = 69.08, c = 65.64 A, beta = 102.7 degrees. Assuming the presence of a monomeric protomer in the asymmetric unit gives a V(M) value of 2.21 A(3) Da(-1) and a solvent content of 44.4%. A cocrystal with NADH, which was isomorphous to the apo form, was also prepared and diffraction data were collected to 1.85 A resolution using Cu Kalpha radiation at 100 K.

| S-EPMC2374150 | biostudies-literature

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