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CSA entry for 1naa
Original Entry
Title:
Oxidoreductase
Compound:
Cellobiose dehydrogenase
Mutant:
No
UniProt/Swiss-Prot:
Q01738-CDH_PHACH
EC Class:
1.1.99.18
Other CSA Entries:
Overview of all sites for 1naa
Homologues of 1naa
Entries for UniProt/Swiss-Prot: Q01738
Entries for EC: 1.1.99.18
Other Databases:
PDB entry: 1naa
PDBsum entry: 1naa
UniProt/Swiss-Prot: Q01738
IntEnz entry: 1.1.99.18
Literature Report:
Introduction:
The oxidoreductase cellobiose dehydrogenase (CDH) from the white-rot fungus
Phanerochaete chrysosporium degrades both lignin and cellulose. It catalyses the oxidation of cellobiose (a reaction product in cellulose hydrolysis) to cellobiono-1,5-lactone. This is used to provide a carbon source for the micro-organism. CDH is the only known extracellular flavocytochrome, a small and heterogeneous group of redox-active proteins that carry both haem and flavin prosthetic groups. Applications of CDH include degradation of various environmental pollutants.
Mechanism:
The generally agreed on mechanism for this reaction is that of the hydride transfer:

1. His 689 acts as a general base by deprotonating the C1 hydroxyl group of the cellobiose substrate, causing hydride transfer from C1 of the substrate to FAD.
2. Asn 732, by hydrogen bonding to O1 of the substrate, facilitates proton transfer to His 689.
3. Tyr 609 hydrogen bonds to a water molecule, increasing the water's affinity for protons, and causing it to deprotonate His 689.
4. This now leaves a reduced FAD (FADH2), the second proton most likely coming from a water molecule.

The mechanism for the oxidation of FADH2 is speculated to be as follows:

1. An internal electron transfer takes place, passing one electron from the flavin centre to the haem, reducing the haem group, and forming a flavin semiquinone.
2. The reduced haem is oxidised by either Fe3+ (to form Fe2+) or superoxide O2-
radical (to form hydrogen peroxide.)
3. The semiquinone reacts with O2 to form the O2- radical, and returns to its initial oxidised state.

Ferrous iron can then be oxidised by hydrogen peroxide to re-form Fe3+, and also
OH- and an OH radical.
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Literature reference 

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
TYRA 609 627Sidechain
ElectrostaticWater
Hydrogen bonds to a water molecule, causing that water molecule to deprotonate the protonated His 689 residue.
Evidence from paper Evidence concerns Evidence type
PubMed ID 12493734 Current protein Residue is positioned appropriately (ligand position known)

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
HISA 689 707Sidechain
Acid/baseSubstrate
Acts as a general base by deprotonating the C1 hydroxyl group, causing hydride transfer to FAD.
Evidence from paper Evidence concerns Evidence type
PubMed ID 12493734 Current protein Structural similarity to homologue of known mechanism
PubMed ID 12493734 Current protein Conservation of residue
PubMed ID 12493734 Current protein Residue is positioned appropriately (ligand position known)

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
ASNA 732 750Sidechain
ElectrostaticSubstrate
Hydrogen bonds to O1 of the substrate, facilitating proton transfer to His 689.
Evidence from paper Evidence concerns Evidence type
PubMed ID 12493734 Current protein Mutagenesis of residue
PubMed ID 12493734 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 12493734 Current protein Structural similarity to homologue of known mechanism
PubMed ID 12493734 Current protein Conservation of residue
Notes:
This is not a definite mechanism, it is merely the most agreed upon.
References:
1
Mechanism of the reductive half-reaction in cellobiose dehydrogenase.
B. M. Hallberg and G. Henriksson and G. Pettersson and A. Vasella and C. Divne
J Biol Chem 278, (9) 7160-6, (2003).
12493734
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