1yb6

From Proteopedia

Hydroxynitrile lyase from hevea brasiliensis in complex with mandelonitrile

PDB ID 1yb6

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Structural highlights

1yb6 is a 1 chain structure with sequence from Hevea brasiliensis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.54Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HNL_HEVBR Involved in cyanogenesis, the release of HCN from injured tissues. Decomposes a varieties of (R) or (S) cyanohydrins into HCN and the corresponding aldehydes and ketones. The natural substrate of this enzyme is (S)-acetone cyanohydrin.

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

The hydroxynitrile lyase from the tropical rubber tree Hevea brasiliensis (HbHNL) is utilized as a biocatalyst in stereospecific syntheses of alpha-hydroxynitriles from aldehydes and methyl-ketones. The catalyzed reaction represents one of the few industrially relevant examples of enzyme mediated C-C coupling reactions. In this work, we determined the X-ray crystal structures (at 1.54 and 1.76 Angstroms resolution) of HbHNL complexes with two chiral substrates -- mandelonitrile and 2,3-dimethyl-2-hydroxy-butyronitrile -- by soaking and rapid freeze quenching techniques. This is the first structural observation of the complex between a HNL and chiral substrates. Consistent with the known selectivity of the enzyme, only the S-enantiomers of the two substrates were observed in the active site. The binding modes of the chiral substrates were identical to that observed for the biological substrate acetone cyanohydrin. This indicates that the transformation of these non-natural substrates follows the same mechanism. A large hydrophobic pocket was identified in the active site of HbHNL which accommodates the more voluminous substituents of the two substrates. A three-point binding mode of the substrates -- hydrophobic pocket, hydrogen bonds between the hydroxyl group and Ser80 and Thr11, electrostatic interaction of the cyano group with Lys236 -- offers a likely structural explanation for the enantioselectivity of the enzyme. The structural data rationalize the observed (S)-enantioselectivity and form the basis for modifying the stereospecificity through rational design. The structures also revealed the necessity of considerable flexibility of the sidechain of Trp128 in order to bind and transform larger substrates.

Structural determinants of the enantioselectivity of the hydroxynitrile lyase from Hevea brasiliensis.,Gartler G, Kratky C, Gruber K J Biotechnol. 2007 Mar 30;129(1):87-97. Epub 2006 Dec 17. PMID:17250917^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gartler G, Kratky C, Gruber K. Structural determinants of the enantioselectivity of the hydroxynitrile lyase from Hevea brasiliensis. J Biotechnol. 2007 Mar 30;129(1):87-97. Epub 2006 Dec 17. PMID:17250917 doi:10.1016/j.jbiotec.2006.12.009