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Overview for MACiE Entry M0141

Version history

General Information

EC Number: 1.17.99.1 (A member of the Oxidoreductases, Acting on CH or CH2 groups, With other acceptors)

Enzyme Name: 4-cresol dehydrogenase (hydroxylating)

Biological Species: Pseudomonas putida (Bacteria)

Catalytic Chain UniprotKB Accession Codes:

  • P09788 - 4-cresol dehydrogenase [hydroxylating] flavoprotein subunit
  • P09787 - 4-cresol dehydrogenase [hydroxylating] cytochrome c subunit

Representative PDB Code: 1dii - CRYSTAL STRUCTURE OF P-CRESOL METHYLHYDROXYLASE AT 2.5 ARESOLUTION (Resolution = 2.50 Å).

Catalytic CATH Codes:

  • 3.40.462.10 - Vanillyl-alcohol Oxidase; Chain A, domain 3
  • 3.30.465.10 - Uridine Diphospho-n-acetylenolpyruvylglucosamine Reductase; domain 3
  • 1.10.45.10 - Vanillyl-alcohol Oxidase; Chain A, domain 4
  • 1.10.760.10 - Cytochrome c

"Other" CATH Codes:

  • 1.10.45.10 - Vanillyl-alcohol Oxidase; Chain A, domain 4
  • 1.10.760.10 - Cytochrome c
  • 3.30.465.10 - Uridine Diphospho-n-acetylenolpyruvylglucosamine Reductase; domain 3

Display structure information

Overall Reaction:

Image of acceptor

Image of 4-cresol

Image of water

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Image of proton

Image of 4-hydroxybenzaldehyde

Image of reduced acceptor

2 acceptor
C00028
CHEBI:17654
4-cresol
C01468
CHEBI:17847
water
C00001
CHEBI:15377
4 proton
C00080
CHEBI:24636
4-hydroxybenzaldehyde
C00633
CHEBI:17597
2 reduced acceptor
C00030

Overall Comment: Work by Cunane et al. [1] suggests that there are a number of alternative proton relay pathways as well as two alternative catalytic bases (Tyr95 or Tyr473). The species which may be involved in the proton pathways are: two buried water molecules Glu427 Glu380 Tyr172 Tyr367 Arg368 Ser289 and Glu286 (which is exposed to the surface). For simplicity here we only considered the shortest pathway i.e. that including Glu380 Tyr367 a water molecule and Glu286. Arg474 stabilises the negative charge that develops at the N1/O2 locus in the hydroquinone and semiquinone forms of flavin during catalysis. Arg474 is linked to Asp167 which in turn is linked to Arg512 to form a hydrogen bonding network that may increase the electropositivity of Arg474 and enhance its ability to stabilise the anionic hydroquinone and semiquinone forms of the flavin [1].


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Stepwise Description of the Reaction

Step 1Proton relay from bulk solvent through Glu177, His436 and Tyr473 to the substrate 4-cresol, resulting in a hydride transfer from the 4-cresol to the cofactor FAD599.
Step 2Glu380 deprotonates water, activating it for a nucleophilic addition to the creosol intermediate. This intermediate is re-protonated via the proton relay chain through Tyr473, His436 and Glu177 to bulk solvent.
Step 3Glu380 is deprotonated through the proton relay chain of Tyr367, water, Glu286 and bulk solvent.
Step 4FAD599 loses a single electron through the Tyr384 covalently attached to the FAD, the main chain carbonyl of Ala649C, side chain of Met650C and the heme cofactor to the external electron acceptor.
Step 5Glu380 deprotonates the activated FAD599, resulting in the second electron transfer through the Tyr384 covalently attached to the FAD, the main chain carbonyl of Ala649C, side chain of Met650C and the heme cofactor to the external electron acceptor.
Step 6Glu380 is deprotonated through the proton relay chain of Tyr367, water, Glu286 and bulk solvent.
Step 7Glu380 deprotonates the intermediate, causing a reduction of the primary alcohol to an aldehyde with concomitant transfer of a hydride to FAD599.
Step 8Glu380 is deprotonated through the proton relay chain of Tyr367, water, Glu286 and bulk solvent.
Step 9FAD599 loses a single electron through the Tyr384 covalently attached to the FAD, the main chain carbonyl of Ala649C, side chain of Met650C and the heme cofactor to the external electron acceptor.
Step 10Glu380 deprotonates the activated FAD599, resulting in the second electron transfer through the Tyr384 covalently attached to the FAD, the main chain carbonyl of Ala649C, side chain of Met650C and the heme cofactor to the external electron acceptor.
Step 11Glu380 is deprotonated through the proton relay chain of Tyr367, water, Glu286 and bulk solvent.

View similar reactions (composite manual annotation)


Catalytic Residues Involved

Type Number Chain Location of Function
Asp 167 A Side Chain
Glu 177 A Side Chain
Glu 286 A Side Chain
Tyr 367 A Side Chain
Glu 380 A Side Chain
Tyr 384 A Side Chain
His 436 A Side Chain
Tyr 473 A Side Chain
Arg 474 A Side Chain
Arg 512 A Side Chain
Ala 649 C Main Chain Carbonyl
Met 650 C Side Chain

Organic Cofactors for M0141

Type Identity Chain
FAD FAD 599 A Overview

Metal Cofactors for M0141

Type Het group Number Chain
iron HEM 699 C Overview

References

  1. L. M. Cunane et al. (2000), J. Mol. Biol., 295, 357-374. Structures of the flavocytochrome p-cresol methylhydroxylase and its enzyme-substrate complex: gated substrate entry and proton relays support the proposed catalytic mechanism.
    Medline: 10623531

Homologue information for M0141 (1dii)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)



Entries with at least one Catalytic CATH code in common (different mechanisms):

MACiE Entry Enzyme Name
EC Number
PDB code CATH code Composite
Reaction Similarity
Catalytic Machinery
Similarity
M0103 vanillyl-alcohol oxidase
1.1.3.38
1vao 3.30.465.10
3.40.462.10
1.10.45.10
0.27840.3957Compare

Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
Link to MetaCyc Link to KEGG Link to BRENDA Link to ExplorENZ
Link to EzCatDB

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catalytic activity (molecular function)
iron ion binding (molecular function)
transport (biological process)
UDP-N-acetylmuramate dehydrogenase activity (molecular function)
electron carrier activity (molecular function)
oxidoreductase activity (molecular function)
oxidoreductase activity, acting on CH-OH group of donors (molecular function)
4-cresol dehydrogenase (hydroxylating) activity (molecular function)
heme binding (molecular function)
electron transport chain (biological process)
metal ion binding (molecular function)
flavin adenine dinucleotide binding (molecular function)
oxidation-reduction process (biological process)
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