6GPK

Crystal structure of human GDP-D-mannose 4,6-dehydratase (E157Q) in complex with GDP-Man

6GPK の概要

• エントリーDOI: 10.2210/pdb6gpk/pdb
• 分子名称: GDP-mannose 4,6 dehydratase, 1,2-ETHANEDIOL, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (6 entities in total)
• 機能のキーワード: gdp-mannose 4, 6 dehydratase, fucosylation, structural genomics, structural genomics consortium, sgc, lyase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 177333.55

構造登録者

Pfeiffer, M.,Krojer, T.,Johansson, C.,von Delft, F.,Bountra, C.,Arrowsmith, C.H.,Edwards, A.,Nidetzky, B.,Oppermann, U.,Structural Genomics Consortium (SGC) (登録日: 2018-06-06, 公開日: 2018-07-18, 最終更新日: 2024-05-15)

主引用文献

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

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: 30984471
DOI: 10.1021/acscatal.9b00064

実験手法

X-RAY DIFFRACTION (1.47 Å)