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The hydroxynitrile lyase from almond: a lyase that looks like an oxidoreductase.

Dreveny I, Gruber K, Glieder A, Thompson A, Kratky C
Structure 9 803-15 (2001)
Cited: 51 times
EuropePMC logo PMID: 11566130

Abstract

Background

Cyanogenesis is a defense process of several thousand plant species. Hydroxynitrile lyase, a key enzyme of this process, cleaves a cyanohydrin into hydrocyanic acid and the corresponding aldehyde or ketone. The reverse reaction constitutes an important tool in biocatalysis. Different classes of hydroxynitrile lyases have convergently evolved from FAD-dependent oxidoreductases, alpha/beta hydrolases, and alcohol dehydrogenases. The FAD-dependent hydroxynitrile lyases (FAD-HNLs) carry a flavin cofactor whose redox properties appear to be unimportant for catalysis.

Results

We have determined the crystal structure of a 61 kDa hydroxynitrile lyase isoenzyme from Prunus amygdalus (PaHNL1) to 1.5 A resolution. Clear electron density originating from four glycosylation sites could be observed. As concerns the overall protein fold including the FAD cofactor, PaHNL1 belongs to the family of GMC oxidoreductases. The active site for the HNL reaction is probably at a very similar position as the active sites in homologous oxidases.

Conclusion

There is strong evidence from the structure and the reaction product that FAD-dependent hydroxynitrile lyases have evolved from an aryl alcohol oxidizing precursor. Since key residues implicated in oxidoreductase activity are also present in PaHNL1, it is not obvious why this enzyme shows no oxidase activity. Similarly, features proposed to be relevant for hydroxy-nitrile lyase activity in other hydroxynitrile lyases, i.e., a general base and a positive charge to stabilize the cyanide, are not obviously present in the putative active site of PaHNL1. Therefore, the reason for its HNL activity is far from being well understood at this point.

Articles - 1ju2 mentioned but not cited (4)

  1. The active site of hydroxynitrile lyase from Prunus amygdalus: modeling studies provide new insights into the mechanism of cyanogenesis. Dreveny I, Kratky C, Gruber K. Protein Sci 11 292-300 (2002)
  2. Crystal Structure of Alcohol Oxidase from Pichia pastoris. Koch C, Neumann P, Valerius O, Feussner I, Ficner R. PLoS One 11 e0149846 (2016)
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  4. Coarse-Graining ddCOSMO through an Interface between Tinker and the ddX Library. Nottoli M, Mikhalev A, Stamm B, Lipparini F. J Phys Chem B 126 8827-8837 (2022)


Reviews citing this publication (6)

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  3. How to overcome limitations in biotechnological processes - examples from hydroxynitrile lyase applications. Andexer JN, Langermann JV, Kragl U, Pohl M. Trends Biotechnol 27 599-607 (2009)
  4. Progress in Stereoselective Construction of C-C Bonds Enabled by Aldolases and Hydroxynitrile Lyases. Liu M, Wei D, Wen Z, Wang JB. Front Bioeng Biotechnol 9 653682 (2021)
  5. Modern Approaches to Discovering New Hydroxynitrile Lyases for Biocatalysis. Padhi SK. Chembiochem 18 152-160 (2017)
  6. Structures of almond hydroxynitrile lyase isoenzyme 5 provide a rationale for the lack of oxidoreductase activity in flavin dependent HNLs. Pavkov-Keller T, Bakhuis J, Steinkellner G, Jolink F, Keijmel E, Birner-Gruenberger R, Gruber K. J Biotechnol 235 24-31 (2016)

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