| Structural highlights
3utd is a 2 chain structure with sequence from Ecoli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Related: | |
| Gene: | ispH, lytB, yaaE, b0029, JW0027 (ECOLI) |
| Activity: | 4-hydroxy-3-methylbut-2-enyl diphosphate reductase, with EC number 1.17.1.2 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[ISPH_ECOLI] Converts 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate into isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Is also involved in penicillin tolerance and control of the stringent response. Seems to directly or indirectly interact with RelA to maintain it in an inactive form during normal growth.[1] [2] [3]
Publication Abstract from PubMed
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, Mossbauer, 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 eta(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.
Discovery of acetylene hydratase activity of the iron-sulphur protein IspH.,Span I, Wang K, Wang W, Zhang Y, Bacher A, Eisenreich W, Li K, Schulz C, Oldfield E, Groll M Nat Commun. 2012 Sep 4;3:1042. doi: 10.1038/ncomms2052. PMID:22948824[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Grawert T, Rohdich F, Span I, Bacher A, Eisenreich W, Eppinger J, Groll M. Structure of active IspH enzyme from Escherichia coli provides mechanistic insights into substrate reduction. Angew Chem Int Ed Engl. 2009;48(31):5756-9. PMID:19569147 doi:10.1002/anie.200900548
- ↑ Grawert T, Span I, Eisenreich W, Rohdich F, Eppinger J, Bacher A, Groll M. Probing the reaction mechanism of IspH protein by x-ray structure analysis. Proc Natl Acad Sci U S A. 2010 Jan 19;107(3):1077-81. Epub 2009 Dec 28. PMID:20080550
- ↑ Span I, Grawert T, Bacher A, Eisenreich W, Groll M. Crystal Structures of Mutant IspH Proteins Reveal a Rotation of the Substrate's Hydroxymethyl Group during Catalysis. J Mol Biol. 2011 Nov 23. PMID:22137895 doi:10.1016/j.jmb.2011.11.033
- ↑ 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. 2012 Sep 4;3:1042. doi: 10.1038/ncomms2052. PMID:22948824 doi:http://dx.doi.org/10.1038/ncomms2052
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