6Q94
Crystal structure of human GDP-D-mannose 4,6-dehydratase (S156D) in complex with GDP-Man
Summary for 6Q94
| Entry DOI | 10.2210/pdb6q94/pdb |
| Descriptor | GDP-mannose 4,6 dehydratase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, GUANOSINE-5'-DIPHOSPHATE-ALPHA-D-MANNOSE, ... (5 entities in total) |
| Functional Keywords | gdp-mannose 4, 6 dehydratase, fucosylation, structural genomics, structural genomics consortium, sgc, lyase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 8 |
| Total formula weight | 331714.02 |
| Authors | Pfeiffer, M.,Krojer, T.,Johansson, C.,von Delft, F.,Bountra, C.,Arrowsmith, C.H.,Edwards, A.,Nidetzky, B.,Oppermann, U.,Structural Genomics Consortium (SGC) (deposition date: 2018-12-17, release date: 2019-04-24, Last modification date: 2024-05-15) |
| Primary citation | Pfeiffer, M.,Johansson, C.,Krojer, T.,Kavanagh, K.L.,Oppermann, U.,Nidetzky, B. A Parsimonious Mechanism of Sugar Dehydration by Human GDP-Mannose-4,6-dehydratase. Acs Catalysis, 9:2962-2968, 2019 Cited by PubMed Abstract: Biosynthesis of 6-deoxy sugars, including l-fucose, involves a mechanistically complex, enzymatic 4,6-dehydration of hexose nucleotide precursors as the first committed step. Here, we determined pre- and postcatalytic complex structures of the human GDP-mannose 4,6-dehydratase at atomic resolution. These structures together with results of molecular dynamics simulation and biochemical characterization of wildtype and mutant enzymes reveal elusive mechanistic details of water elimination from GDP-mannose C5″ and C6″, coupled to NADP-mediated hydride transfer from C4″ to C6″. We show that concerted acid-base catalysis from only two active-site groups, Tyr and Glu, promotes a 1,4-elimination from an enol (not an enolate) intermediate. We also show that the overall multistep catalytic reaction involves the fewest position changes of enzyme and substrate groups and that it proceeds under conserved exploitation of the basic (minimal) catalytic machinery of short-chain dehydrogenase/reductases. PubMed: 30984471DOI: 10.1021/acscatal.9b00064 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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