A parsimonious mechanism of sugar dehydration by human GDP-mannose-4,6-dehydratase
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, Tyr179 and Glu157, promotes a syn 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
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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ACS catalysis. - 9, 4 (2019) , 2962-2968, ISSN: 2155-5435
- Keyword
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Kohlenhydrate
Enzymkatalyse
Reaktionsmechanismus
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2020
- Creator
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Pfeiffer, Martin
Johansson, Catrine
Krojer, Tobias
Kavanagh, Kathryn L.
Oppermann, Udo
Nidetzky, Bernd
- Contributor
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FRIAS Natur- und Lebenswissenschaften, Medizin und Ingenieurwissenschaften
- DOI
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10.1021/acscatal.9b00064
- URN
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urn:nbn:de:bsz:25-freidok-1526740
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:27 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Pfeiffer, Martin
- Johansson, Catrine
- Krojer, Tobias
- Kavanagh, Kathryn L.
- Oppermann, Udo
- Nidetzky, Bernd
- FRIAS Natur- und Lebenswissenschaften, Medizin und Ingenieurwissenschaften
- Universität
Time of origin
- 2020
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Robust Implementation of a Parsimonious Dynamic Factor Model to Nowcast GDP
Going beyond GDP with a parsimonious indicator: Inequality-adjusted healthy lifetime income
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Cell-free enzymatic synthesis of GDP-l-fucose from mannose
Characterization of GMPP from Dendrobium huoshanense yielding GDP-D-mannose
Structural insights into selective inhibition of leishmanial GDP-mannose pyrophosphorylase
Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase
Ubiquitination contributes to the regulation of GDP-mannose pyrophosphorylase B activity
Parsimonious Histograms
1H-Tetrazole as Catalyst in Phosphomorpholidate Coupling Reactions : Efficient Synthesis of GDP-Fucose, GDP-Mannose, and UDP-Galactose
5-Aminolaevulinsäure-Dehydratase [Aminolaevulinsäure-Dehydratase] im normalen Blut
Robust Implementation of a Parsimonious Dynamic Factor Model to Nowcast GDP
Going beyond GDP with a parsimonious indicator: Inequality-adjusted healthy lifetime income
Going Beyond GDP with a Parsimonious Indicator: Inequality-Adjusted Healthy Lifetime Income
Going beyond GDP with a parsimonious indicator : inequality-adjusted healthy lifetime income
Cell-free enzymatic synthesis of GDP-l-fucose from mannose
Characterization of GMPP from Dendrobium huoshanense yielding GDP-D-mannose
Structural insights into selective inhibition of leishmanial GDP-mannose pyrophosphorylase
Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase
Ubiquitination contributes to the regulation of GDP-mannose pyrophosphorylase B activity
Parsimonious Histograms
1H-Tetrazole as Catalyst in Phosphomorpholidate Coupling Reactions : Efficient Synthesis of GDP-Fucose, GDP-Mannose, and UDP-Galactose