User:BogBot/Test
| nitrile hydratase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC no. | 4.2.1.84 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
| |||||||||
In enzymology, nitrile hydratases (NHases; EC 4.2.1.84) are mononuclear iron or non-corrinoid cobalt enzymes that catalyse the hydration of diverse nitriles to their corresponding amides
R-C≡N + H2O → R-C(O)NH2
Metal cofactor[edit]
Cobalt is a toxic compound for humans and most organisms. In biochemistry, cobalt is generally found only in a corrin ring, such as vitamin B12. Nitrile hydratase is one of the rare enzymes that uses cobalt directly as a cofactor. The mechanism by which the cobalt is transported to NHase without causing toxicity is unclear, although a cobalt permease has been identified, which transports cobalt across the cell membrane.
Metabolic pathway[edit]
Nitrile hydratase and amidase are the two hydrolytic enzymes responsible for the sequential metabolism of nitriles in some bacteria and fungi which are capable of utilising aliphatic nitriles as the sole source of nitrogen and carbon.
Industrial applications[edit]
NHases have been efficiently used for the industrial production of acrylamide from acrylonitrile and for removal of nitriles from wastewater. Photosensitive NHases intrinsically possess nitric oxide (NO) bound to the iron centre and its photodissociation activates the enzyme.
Structure[edit]
NHases are composed of two types of subunits, α and β, which are not related in amino acid sequence. NHases exist as αβ dimers or α2β2 tetramers and bind one metal atom per αβ unit. The 3-D structures of a number of NHases have been determined. The α subunit consists of a long extended N-terminal "arm", containing two α-helices, and a C-terminal domain with an unusual four-layered structure (α-β-β-α). The β subunit consists of a long N-terminal loop that wraps around the α subunit; a helical domain that packs with N-terminal domain of the α subunit; and a C-terminal domain consisting of a β-roll and one short helix.
Enzymatic mechanism[edit]
The metal centre is located in the central cavity at the interface between two subunits. All protein ligands to the metal atom are provided by the α subunit. The protein ligands to the iron are the sidechains of the three cysteine (Cys) residues and two mainchain amide nitrogens. The metal ion is octahedrally coordinated, with the protein ligands at the five vertices of an octahedron. The sixth position, accessible to the active site cleft, is occupied either by NO or by a solvent-exchangeable ligand (hydroxide or water). The two Cys residues coordinated to the metal are post-translationally modified to Cys-sulfinic (Cys-SO2H) and -sulfenic (Cys-SOH) acids.
References[edit]
Structural links[edit]
- PDB: 1IRE - crystal structure of Co-NHase from Pseudonocardia thermophila
- PDB: 2AHJ - crystal structure of Fe-NHase from Rhodococcus erythropolis complexed with nitric oxide
- InterPro: IPR004232 - InterPro entry for nitrile hydratase alpha subunit
- InterPro: IPR003168 - InterPro entry for nitrile hydratase beta subunit