GDP-D-mannose dehydratase [Cell wall/membrane/envelope biogenesis].

GDP-mannose 4,6 dehydratase.

GDP-mannose 4,6 dehydratase, extended (e) SDRs. GDP-mannose 4,6 dehydratase, a homodimeric SDR, catalyzes the NADP(H)-dependent conversion of GDP-(D)-mannose to GDP-4-keto, 6-deoxy-(D)-mannose in the fucose biosynthesis pathway. These proteins have the canonical active site triad and NAD-binding pattern, however the active site Asn is often missing and may be substituted with Asp. A Glu residue has been identified as an important active site base. Extended SDRs are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif.

GDP-mannose 4,6-dehydratase. Alternate name: GDP-D-mannose dehydratase. This enzyme converts GDP-mannose to GDP-4-dehydro-6-deoxy-D-mannose, the first of three steps for the conversion of GDP-mannose to GDP-fucose in animals, plants, and bacteria. In bacteria, GDP-L-fucose acts as a precursor of surface antigens such as the extracellular polysaccharide colanic acid of E. coli. Excluded from this model are members of the clade that score poorly because of highly dervied (phylogenetically long-branch) sequences, e.g. Aneurinibacillus thermoaerophilus Gmd, described as a bifunctional GDP-mannose 4,6-dehydratase/GDP-6-deoxy-D-lyxo-4-hexulose reductase (PUBMED:11096116). [Cell envelope, Biosynthesis and degradation of surface polysaccharides and lipopolysaccharides]

GDP-mannose 4,6-dehydratase

Crystalstructure of GDP-mannose 4,6-dehydratase from Brucella abortus (strain 2308) in complex with Guanosine-diphosphate-rhamnose [Brucella abortus 2308],7KF3_B Crystal structure of GDP-mannose 4,6-dehydratase from Brucella abortus (strain 2308) in complex with Guanosine-diphosphate-rhamnose [Brucella abortus 2308],7KF3_C Crystal structure of GDP-mannose 4,6-dehydratase from Brucella abortus (strain 2308) in complex with Guanosine-diphosphate-rhamnose [Brucella abortus 2308],7KF3_D Crystal structure of GDP-mannose 4,6-dehydratase from Brucella abortus (strain 2308) in complex with Guanosine-diphosphate-rhamnose [Brucella abortus 2308]

CrystalStructure of GDP-D-Mannose Dehydratase from Aquifex aeolicus VF5 [Aquifex aeolicus VF5],2Z1M_B Crystal Structure of GDP-D-Mannose Dehydratase from Aquifex aeolicus VF5 [Aquifex aeolicus VF5],2Z1M_C Crystal Structure of GDP-D-Mannose Dehydratase from Aquifex aeolicus VF5 [Aquifex aeolicus VF5],2Z1M_D Crystal Structure of GDP-D-Mannose Dehydratase from Aquifex aeolicus VF5 [Aquifex aeolicus VF5],2Z95_A Crystal Structure of GDP-D-Mannose Dehydratase from Aquifex aeolicus VF5 [Aquifex aeolicus],2Z95_B Crystal Structure of GDP-D-Mannose Dehydratase from Aquifex aeolicus VF5 [Aquifex aeolicus],2Z95_C Crystal Structure of GDP-D-Mannose Dehydratase from Aquifex aeolicus VF5 [Aquifex aeolicus],2Z95_D Crystal Structure of GDP-D-Mannose Dehydratase from Aquifex aeolicus VF5 [Aquifex aeolicus]

E.ColiGdp-Mannose 4,6-Dehydratase [Escherichia coli]

CrystalStructure of GDP-mannose 4,6 dehydratase bound to a GDP-fucose based inhibitor [Homo sapiens],5IN4_B Crystal Structure of GDP-mannose 4,6 dehydratase bound to a GDP-fucose based inhibitor [Homo sapiens],5IN4_C Crystal Structure of GDP-mannose 4,6 dehydratase bound to a GDP-fucose based inhibitor [Homo sapiens],5IN4_D Crystal Structure of GDP-mannose 4,6 dehydratase bound to a GDP-fucose based inhibitor [Homo sapiens],5IN5_A Crystal Structure of GDP-mannose 4,6 dehydratase in complex with natural inhibitor GDP-Fucose [Homo sapiens],5IN5_B Crystal Structure of GDP-mannose 4,6 dehydratase in complex with natural inhibitor GDP-Fucose [Homo sapiens],5IN5_C Crystal Structure of GDP-mannose 4,6 dehydratase in complex with natural inhibitor GDP-Fucose [Homo sapiens],5IN5_D Crystal Structure of GDP-mannose 4,6 dehydratase in complex with natural inhibitor GDP-Fucose [Homo sapiens]

Crystalstructure of a GDP-mannose dehydratase from Naegleria fowleri [Naegleria fowleri]

GDP-mannose 4,6 dehydratase OS=Drosophila melanogaster OX=7227 GN=Gmd PE=1 SV=2

GDP-mannose 4,6-dehydratase OS=Rhizobium fredii (strain HH103) OX=1117943 GN=gmd PE=3 SV=1

GDP-mannose 4,6-dehydratase OS=Sinorhizobium fredii (strain NBRC 101917 / NGR234) OX=394 GN=gmd PE=3 SV=1

GDP-mannose 4,6-dehydratase OS=Escherichia coli O6:H1 (strain CFT073 / ATCC 700928 / UPEC) OX=199310 GN=gmd PE=3 SV=1

GDP-mannose 4,6-dehydratase OS=Escherichia coli (strain K12) OX=83333 GN=gmd PE=1 SV=1