P-(S)-hydroxymandelonitrile lyase
Hydroxynitrile lyases (HNLs) constitute a diverse family of enzymes that catalyse the stereospecific cleavage of a wide range of cyanohydrins into aldehydes or ketones and hydrogen cyanide from injured tissues. It is also involved in the catabolism of the cyanogenic glycoside dhurrin.
The release of HCN is a common defense of food plants against herbivores. The HNL of Sorghum bicolor (SbHNL) has no similarity to other HNLs except in function.
This protein is a member of the Alpha/Beta hydrolase fold superfamily.
Reference Protein and Structure
- Sequence
-
P52708
(4.1.2.11)
(Sequence Homologues)
(PDB Homologues)
- Biological species
-
Sorghum bicolor (sorghum)
- PDB
-
1gxs
- Crystal Structure of Hydroxynitrile Lyase from Sorghum bicolor in Complex with Inhibitor Benzoic Acid: a novel cyanogenic enzyme
(2.3 Å)
- Catalytic CATH Domains
-
3.40.50.1820
(see all for 1gxs)
Enzyme Reaction (EC:4.1.2.11)
→
+
Alternative enzyme names: Sorghum hydroxynitrile lyase, Hydroxynitrile lyase, Oxynitrilase, (S)-4-hydroxymandelonitrile hydroxybenzaldehyde-lyase,
Enzyme Mechanism
Introduction
The mechanism has been proposed to be E2 elimination of HCN from the hydroxynitrile group by:
- Deprotonation of the substrate hydroxy group (activated by hydrogen bonding with Ser 158) by the carboxylate group of the C-terminal Trp 270, with concurrent formation of the C=O double bond and loss of cyanide.
- Proton transfer from Trp 270 to cyanide via an active site water molecule.
Catalytic Residues Roles
| UniProt | PDB* (1gxs) | ||
| Trp325 (C-term) | Trp270A (C-term) | Deprotonates the hydroxynitrile using the C-terminus carboxylate. This proton is later transferred to the active site water as the water transfers another proton to cyanide. | proton shuttle (general acid/base) |
| Ser213 | Ser158A | Hydrogen bonds to the substrate hydroxyl group (which becomes a carbonyl). This makes the substrate more acidic and stabilises the charge on the transition state. | modifies pKa, electrostatic stabiliser |
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file;
y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain;
C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.
Chemical Components
References
- Lauble H et al. (2002), Biochemistry, 41, 12043-12050. Crystal structure of hydroxynitrile lyase from Sorghum bicolor in complex with the inhibitor benzoic acid: a novel cyanogenic enzyme. DOI:10.2210/pdb1gxs/pdb. PMID:12356304.
Catalytic Residues Roles
| Residue | Roles |
|---|---|
| Trp270A (C-term) | proton shuttle (general acid/base) |
| Ser158A | electrostatic stabiliser, modifies pKa |