3UV3

Ec_IspH in complex with but-2-ynyl diphosphate (1086)

Summary for 3UV3

• Entry DOI: 10.2210/pdb3uv3/pdb
• Related: 3DNF 3KE8 3UTC 3UV6 3UV7 3UV8 3UWM 3urk 3utd
• Descriptor: 4-hydroxy-3-methylbut-2-enyl diphosphate reductase, IRON/SULFUR CLUSTER, but-2-yn-1-yl trihydrogen diphosphate, ... (4 entities in total)
• Functional Keywords: iron-sulfur protein, isph, lytb, isoprenoid biosynthesis, non-mevalonate pathway, oxidoreductase
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 72744.40

Authors

Span, I.,Wang, K.,Wang, W.,Zhang, Y.,Bacher, A.,Eisenreich, W.,Schulz, C.,Oldfield, E.,Groll, M. (deposition date: 2011-11-29, release date: 2012-09-05, Last modification date: 2023-09-13)

Primary citation

Span, I.,Wang, K.,Wang, W.,Zhang, Y.,Bacher, A.,Eisenreich, W.,Li, K.,Schulz, C.,Oldfield, E.,Groll, M.
Discovery of acetylene hydratase activity of the iron-sulphur protein IspH.
Nat Commun, 3:1042-1042, 2012

PubMed Abstract: The final step of the methylerythritol phosphate isoprenoid biosynthesis pathway is catalysed by the iron-sulphur enzyme IspH, producing the universal precursors of terpenes: isopentenyl diphosphate and dimethylallyl diphosphate. Here we report an unforeseen reaction discovered during the investigation of the interaction of IspH with acetylene inhibitors by X-ray crystallography, Mößbauer, and nuclear magnetic resonance spectroscopy. In addition to its role as a 2H(+)/2e(-) reductase, IspH can hydrate acetylenes to aldehydes and ketones via anti-Markovnikov/Markovnikov addition. The reactions only occur with the oxidised protein and proceed via η(1)-O-enolate intermediates. One of these is characterized crystallographically and contains a C4 ligand oxygen bound to the unique, fourth iron in the 4Fe-4S cluster: this intermediate subsequently hydrolyzes to produce an aldehyde product. This unexpected side to IspH reactivity is of interest in the context of the mechanism of action of other acetylene hydratases, as well as in the design of antiinfectives targeting IspH.

PubMed: 22948824
DOI: 10.1038/ncomms2052

Experimental method

X-RAY DIFFRACTION (1.6 Å)