Information on EC 4.2.1.168 - GDP-4-dehydro-6-deoxy-alpha-D-mannose 3-dehydratase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
4.2.1.168
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RECOMMENDED NAME
GeneOntology No.
GDP-4-dehydro-6-deoxy-alpha-D-mannose 3-dehydratase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
2-GDP-[(2S,3S,6R)-5-amino-6-methyl-3,6-dihydro-2H-pyran-3-ol] = 2-GDP-[(2S,3S,6R)-5-imino-6-methyloxan-3-ol]
show the reaction diagram
(1b), spontaneous
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GDP-2-[(2S,3S,6R)-5-imino-6-methyloxan-3-ol] + H2O = GDP-4-dehydro-3,6-dideoxy-alpha-D-mannose + ammonia
show the reaction diagram
(1c), spontaneous
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GDP-4-dehydro-alpha-D-rhamnose + L-glutamate = 2-GDP-[(2S,3S,6R)-5-amino-6-methyl-3,6-dihydro-2H-pyran-3-ol] + 2-oxoglutarate + H2O
show the reaction diagram
(1a)
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GDP-4-dehydro-alpha-D-rhamnose + L-glutamate = GDP-4-dehydro-3,6-dideoxy-alpha-D-mannose + 2-oxoglutarate + ammonia
show the reaction diagram
overall reaction
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SYSTEMATIC NAME
IUBMB Comments
GDP-4-dehydro-alpha-D-rhamnose 3-hydro-lyase
This enzyme, involved in beta-L-colitose biosynthesis, is a unique vitamin-B6-dependent enzyme. In the first step of catalysis, the bound pyridoxal phosphate (PLP) cafactor is transaminated to the pyridoxamine 5'-phosphate (PMP) form of vitamin B6, using L-glutamate as the amino group donor. The PMP cofactor then forms a Schiff base with the sugar substrate and the resulting adduct undergoes a 1,4-dehydration to eliminate the 3-OH group. Hydrolysis of the product from the enzyme restores the PLP cofactor and results in the release of an unstable enamine intermediate. This intermediate tautomerizes to form an imine form, which hydrolyses spontaneously, releasing ammonia and forming the final product.
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
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enzyme catalyzes the third step in the pathway to colitose, namely the PLP-dependent removal of the C3'-hydroxyl group from GDP-4-keto-6-deoxymannose
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
GDP-4-dehydro-alpha-D-rhamnose + L-glutamate
GDP-4-dehydro-3,6-dideoxy-alpha-D-mannose + 2-oxoglutarate + ammonia
show the reaction diagram
GDP-D-perosamine + L-glutamate
GDP-4-dehydro-3,6-dideoxymannose + 2-oxoglutarate + ammonia
show the reaction diagram
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wild-type ColD is able to catalyze the production of GDP-4-keto-3,6-dideoxymannose using GDP-perosamine instead of GDP-4-keto-6-deoxymannose as a substrate
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additional information
?
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enzyme functions as GDP-4-keto-6-deoxy-D-mannose-3-dehydrase responsible for C-3 deoxygenation of GDP-4-keto-6-deoxy-D-mannose. The enzyme is coenzyme B6-dependent and catalysis is initiated by a transamination step in which pyridoxal 5'-phosphate is converted to pyridoxamine 5'-phosphate in the presene of L-glutamate. This coenzyme forms a Schiff base with the keto sugar substrate and the resulting adduct undergoes a pyridoxamine 5'-phosphate-mediated beta-dehydration reaction to give a sugar enamine intermediate, which after tautomerization and hydrolysis to release ammonia yields GDP-4-keto-3,6-dideoxy-D-mannose as the product
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
pyridoxamine 5'-phosphate
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Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
H188N mutant with bound GDP-perosamine, to 1.7 A resolution. The sugar analog is trapped in the active site as an external aldimine. The active site is positioned between the two subunits of the dimer. The diphosphoryl groups of the ligand are anchored to the protein via Arg219 and Arg331, the hydroxyl groups of the hexose only lie within hydrogen bonding distance to ordered water molecules. The hexose moiety of the ligand adopts a boat rather than the typically observed chair conformation
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mutant H188K in the presence of alpha-ketoglutarate and pyridoxal 5'-phosphate, to 1.9 A resolution. The observed electron density is consistent with the formation of a geminal diamine intermediate formed by the reaction of an internal aldimine with glutamate
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the two subunits of the protein form a tight dimer. The PLP-binding pocket is formed primarily by one subunit, with a loop from Phe 240 to Glu 253 in the second subunit, that completes the active site architecture. The hydrated form of PLP is observed. Amino acid residues involved in anchoring the cofactor to the protein include Gly56, Ser57, Asp159, Glu162, and Ser183 from one subunit and Asn248 from the second monomer. His188 is the active site base required for catalysis
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE