| Structural highlights
Function
[HNL_ARATH] Involved in cyanogenesis, the release of HCN from injured tissues (By similarity). Displays R-selective hydroxynitrile lyase activity. Also accepts nitromethane (MeNO2) as a donor in a reaction with aromatic aldehydes to yield (R)-beta-nitro alcohols.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Hydroxynitrile lyases (HNLs) catalyze the cleavage of cyanohydrins to yield hydrocyanic acid (HCN) and the respective carbonyl compound and are key enzymes in the process of cyanogenesis in plants. In organic syntheses, HNLs are used as biocatalysts for the formation of enantiopure cyanohydrins. We determined the structure of the recently identified, R-selective HNL from Arabidopsis thaliana (AtHNL) at a crystallographic resolution of 2.5 A. The structure exhibits an alpha/beta-hydrolase fold, very similar to the homologous, but S-selective, HNL from Hevea brasiliensis (HbHNL). The similarities also extend to the active sites of these enzymes, with a Ser-His-Asp catalytic triad present in all three cases. In order to elucidate the mode of substrate binding and to understand the unexpected opposite enantioselectivity of AtHNL, complexes of the enzyme with both (R)- and (S)-mandelonitrile were modeled using molecular docking simulations. Compared to the complex of HbHNL with (S)-mandelonitrile, the calculations produced an approximate mirror image binding mode of the substrate with the phenyl rings located at very similar positions, but with the cyano groups pointing in opposite directions. A catalytic mechanism for AtHNL is proposed, in which His236 from the catalytic triad acts as a general base and the emerging negative charge on the cyano group is stabilized by main-chain amide groups and an alpha-helix dipole very similar to alpha/beta-hydrolases. This mechanistic proposal is additionally supported by mutagenesis studies.
Hydroxynitrile lyases with alpha/beta-hydrolase fold: two enzymes with almost identical 3D structures but opposite enantioselectivities and different reaction mechanisms.,Andexer JN, Staunig N, Eggert T, Kratky C, Pohl M, Gruber K Chembiochem. 2012 Sep 3;13(13):1932-9. doi: 10.1002/cbic.201200239. Epub 2012 Jul, 31. PMID:22851196[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yang Y, Xu R, Ma CJ, Vlot AC, Klessig DF, Pichersky E. Inactive methyl indole-3-acetic acid ester can be hydrolyzed and activated by several esterases belonging to the AtMES esterase family of Arabidopsis. Plant Physiol. 2008 Jul;147(3):1034-45. doi: 10.1104/pp.108.118224. Epub 2008 May, 8. PMID:18467465 doi:http://dx.doi.org/10.1104/pp.108.118224
- ↑ Guterl JK, Andexer JN, Sehl T, von Langermann J, Frindi-Wosch I, Rosenkranz T, Fitter J, Gruber K, Kragl U, Eggert T, Pohl M. Uneven twins: comparison of two enantiocomplementary hydroxynitrile lyases with alpha/beta-hydrolase fold. J Biotechnol. 2009 May 20;141(3-4):166-73. doi: 10.1016/j.jbiotec.2009.03.010., Epub 2009 Mar 27. PMID:19433222 doi:http://dx.doi.org/10.1016/j.jbiotec.2009.03.010
- ↑ Fuhshuku K, Asano Y. Synthesis of (R)-beta-nitro alcohols catalyzed by R-selective hydroxynitrile lyase from Arabidopsis thaliana in the aqueous-organic biphasic system. J Biotechnol. 2011 May 20;153(3-4):153-9. doi: 10.1016/j.jbiotec.2011.03.011., Epub 2011 Mar 23. PMID:21439333 doi:http://dx.doi.org/10.1016/j.jbiotec.2011.03.011
- ↑ Andexer J, von Langermann J, Mell A, Bocola M, Kragl U, Eggert T, Pohl M. An R-selective hydroxynitrile lyase from Arabidopsis thaliana with an alpha/beta-hydrolase fold. Angew Chem Int Ed Engl. 2007;46(45):8679-81. PMID:17907254 doi:http://dx.doi.org/10.1002/anie.200701455
- ↑ Andexer JN, Staunig N, Eggert T, Kratky C, Pohl M, Gruber K. Hydroxynitrile lyases with alpha/beta-hydrolase fold: two enzymes with almost identical 3D structures but opposite enantioselectivities and different reaction mechanisms. Chembiochem. 2012 Sep 3;13(13):1932-9. doi: 10.1002/cbic.201200239. Epub 2012 Jul, 31. PMID:22851196 doi:http://dx.doi.org/10.1002/cbic.201200239
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