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Overview for MACiE Entry M0227

Version history

General Information

EC Number: 1.1.1.271 (A member of the Oxidoreductases, Acting on the CH-OH group of donors, With NAD+ or NADP+ as acceptor)

Enzyme Name: GDP-L-fucose synthase

Biological Species: Escherichia coli (Bacteria)

Catalytic Chain UniprotKB Accession Codes:

  • P32055 - GDP-L-fucose synthase

Representative PDB Code: 1e6u - GDP 4-KETO-6-DEOXY-D-MANNOSE EPIMERASE REDUCTASE (Resolution = 1.45 Å).

Catalytic CATH Codes:

Display structure information

Overall Reaction:

Image of NADPH

Image of GDP-4-dehydro-6-deoxy-D-mannose

Image of Proton

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Image of NADP

Image of GDP-L-fucose

NADPH
C00005
CHEBI:16474
GDP-4-dehydro-6-deoxy-D-mannose
C01222
CHEBI:16955
Proton
C00080
CHEBI:24636
NADP
C00006
CHEBI:18009
GDP-L-fucose
C14830
CHEBI:17009

Overall Comment: The epimerisation reactions can occur with or without NADPH being bound to the enzyme. However, upon binding of NADPH the reaction efficiency increases due to changes in the structure of the active site. Both Cys109 and His179 have been proposed as the general acid/base catalyst in the removal of the C3 and C5 protons during epimerisation, due to the fact that mutation of both these residues significantly reduces catalytic activity, but not substrate binding. There is, as of yet, no clear evidence for either Cys109 of His179. We have taken His179 to be the base in this reaction based upon the fact that it is more highly conserved than Cys109 [1].


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Stepwise Description of the Reaction

Step 1His179 initiates a keto-enol tautomerisation by removing the C3 proton of the substrate, forming an enolic intermediate and resulting in concomitant protonation of the C4 oxygen by Tyr136.
Step 2Tyr136 initiates a keto-enol tautomerisation by removing the O4 proton, forming the keto form and protonation of C3 by His179 completes the epimerisation of the substrate, i.e. the proton is added to the opposite side of the ring from which it was removed.
Step 3His179 removes the C5 proton leading to the formation of an enolic intermediate and protonation of the C4 oxygen by Tyr136.
Step 4Tyr136 deprotonates the substrate at O4 leading to the formation of the keto form and protonation of C5 by His179. This proton is added on the opposite side of the ring from which it was removed.
Step 5NADPH transfers a hydride from its C4 position to the C4 position of the sugar. The resulting alkoxide is protonated by Tyr136, which is in turn protonated by Ser107.
Step 6Inferred return step in which Ser107 is re-protonated by water.

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Catalytic Residues Involved

Type Number Chain Location of Function
Tyr 136 A Side Chain
Lys 140 A Side Chain
Ser 107 A Side Chain
Ser 108 A Side Chain
Cys 109 A Side Chain
His 179 A Side Chain

References

  1. C. Rosano et al. (2000), J. Mol. Biol., 303, 77-91. Probing the catalytic mechanism of GDP-4-keto-6-deoxy-d-mannose Epimerase/Reductase by kinetic and crystallographic characterization of site-specific mutants.
    Medline: 11021971
  2. W. S. Somers et al. (1998), Structure, 6, 1601-1612. GDP-fucose synthetase from Escherichia coli: structure of a unique member of the short-chain dehydrogenase/reductase family that catalyzes two distinct reactions at the same active site.
    Medline: 9862812

Homologue information for M0227 (1e6u)

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
M0255 alcohol dehydrogenase
1.1.1.1
1mg5 3.40.50.720
0.24030.5142Compare
M0092 UDP-glucose 6-dehydrogenase
1.1.1.22
1dli 3.40.50.720
0.67790.1499Compare
M0021 malate dehydrogenase (oxaloacetate-decarboxylating)
1.1.1.38
1do8 3.40.50.720
0.4690.1741Compare
M0110 D-amino-acid oxidase
1.4.3.3
1c0p 3.40.50.720
0.48830.1999Compare
M0237 pteridine reductase
1.5.1.33
2c7v 3.40.50.720
0.60970.09Compare
M0116 NAD(P)+ transhydrogenase (AB-specific)
1.6.1.2
1hzz 3.40.50.720
0.250.0898Compare
M0142 ferredoxin-NADP+ reductase
1.18.1.2
1e6e 3.40.50.720
0.14810.0818Compare
M0090 adenosylhomocysteinase
3.3.1.1
1b3r 3.40.50.720
0.65280.3992Compare
M0226 UDP-sulfoquinovose synthase
3.13.1.1
1qrr 3.40.50.720
3.90.25.10
0.67820.5875Compare
M0228 dTDP-glucose 4,6-dehydratase
4.2.1.46
1bxk 3.40.50.720
3.90.25.10
0.71420.2164Compare
M0188 UDP-glucose 4-epimerase
5.1.3.2
1xel 3.40.50.720
3.90.25.10
0.32750.5142Compare

View a comparison of the other reactions in MACiE with the CATH domain 3.40.50.720

View a comparison of the other reactions in MACiE with the CATH domain 3.90.25.10


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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