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Catalytic Site Atlas

CSA LITERATURE entry for 1g72

E.C. namemethanol dehydrogenase (cytochrome c)
SpeciesMethylophilus methylotrophus (Bacteria)
E.C. Number (IntEnz) 1.1.2.7
CSA Homologues of 1g72There are 40 Homologs
CSA Entries With UniProtID P38539
CSA Entries With EC Number 1.1.2.7
PDBe Entry 1g72
PDBSum Entry 1g72
MACiE Entry M0099

Literature Report

IntroductionMethanol dehydrogenase (MEDH) is a periplasmic quinoprotein. It catalyses the oxidation of methanol and other small alcohols to the corresponding aldehyde with the release of two protons and two electrons. The enzyme uses the pyrroloquinolinequinone (PQQ) cofactor.
MEDH is an H2L2 heterotetramer, made of two heavy (H) chains and two light (L) chains. Each H subunit contains one molecule of the prosthetic group PQQ, which is non-covalently bound to the polypeptide chain, as well as one calcium ion which is catalytically essential. There is no interaction between the L chains which fold around the surface of the H chains.
MechansimThere has been some debate over the mechanism of MEDH, however, it is now thought that a hydride transfer is employed rather than an addition-elimination reaction. The reaction is initiated by the abstraction of a proton from the alcohol substrate by the general base Glu117. Simultaneously, a hydride is transferred to C'5 of PQQ, forming PQQH-. The aldehyde product then leaves the active site via an unknown pathway. The proton from Glu171 is transferred to Asp297, where it is positioned correctly to be abstracted by the alkoxide of PQQH-, forming PQQH. Quantum mechanical modelling then suggests Glu171 acts as a general base through a water molecule to initiate enolisation of PQQH to PQQH2. The presence of a calcium divalent cation within the active site polarises the PQQ carbonyl towards accepting a hydride.
Reaction

Catalytic Sites for 1g72

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluA171173macie:sideChainThe residue is correctly positioned within the active site to act as a general base towards the alcohol substrate, initiating hydride transfer. It is thought to relay its attained proton to Asp297 which is positioned to act as a general acid to the alkoxide of PQQH-. The carboxylate anion of Glu171 is then thought to initiate enolisation of the PQQH prosthetic group to PQQH2 through a water molecule.
AspA297299macie:sideChainIn the hydride mechanism, Asp297 is thought to act as a general acid to the PQQH- alkoxide anion, donating a proton relayed from Glu171. Modelling studies have ruled out Asp297 as the general base to initiate hydride transfer, although this has been suggested by structural data.

Literature References

Notes:
Reddy SY
Determination of enzyme mechanisms by molecular dynamics: studies on quinoproteins, methanol dehydrogenase, and soluble glucose dehydrogenase.
Protein Sci 2004 13 1965-1978
PubMed: 15273299
Anthony C
The structure and function of methanol dehydrogenase and related quinoproteins containing pyrrolo-quinoline quinone.
Biochem J 1994 304 ( Pt 3) 665-674
PubMed: 7818466
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