Deuterolysin
Deuterolysin is a zinc metalloproteinase, part of a novel family of zinc metalloproteinases which have an Asp residue as the third zinc binding ligand in addition to the general sequence HEXXH found in all zinc metalloproteinases. It shows a preference for basic protein substrates such as histones, and is of particular importance in the Japanese fermentation industry.
Reference Protein and Structure
- Sequence
-
P46076
(3.4.24.39)
(Sequence Homologues)
(PDB Homologues)
- Biological species
-
Aspergillus oryzae RIB40 (Fungus)
- PDB
-
1eb6
- Deuterolysin from Aspergillus oryzae
(1.0 Å)
- Catalytic CATH Domains
-
3.40.390.10
(see all for 1eb6)
- Cofactors
- Zinc(2+) (1)
Enzyme Reaction (EC:3.4.24.39)
+
→
+
Alternative enzyme names: Penicillium roqueforti metalloproteinase, Penicillium roqueforti protease II, Acid metalloproteinase, Microbial neutral proteinase II, Neutral proteinase II,
Enzyme Mechanism
Introduction
Glu 129 and Zn together act to activate a water molecule so that it can act as a nucleophile to attack the peptide substrate. This forms a tetrahedral intermediate, stabilised by proton donation by Tyr 106, which then collapses to release the products.
Catalytic Residues Roles
| UniProt | PDB* (1eb6) | ||
| His303, His307, Asp318 | His128A, His132A, Asp143A | Form Zinc binding site | metal ligand |
| Tyr281 | Tyr106A | Donates proton to the oxyanion of the tetrahedral intermediate to stabilise the transition state. | electrostatic stabiliser |
| Glu304 | Glu129A | Accepts a proton from water to activate it for nucleophilic attack on the peptide substrate, forming the tetrahedral intermediate. | 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
- Fushimi N et al. (1999), J Biol Chem, 274, 24195-24201. Aspzincin, a Family of Metalloendopeptidases with a New Zinc-binding Motif: IDENTIFICATION OF NEW ZINC-BINDING SITES (His128, His132, and Asp164) AND THREE CATALYTICALLY CRUCIAL RESIDUES (Glu129, Asp143, and Tyr106) OF DEUTEROLYSIN FROMASPERGILLUS ORYZAE BY SITE-DIRECTED MUTAGENESIS. DOI:10.1074/jbc.274.34.24195. PMID:10446194.
- McAuley KE et al. (2001), Acta Crystallogr D Biol Crystallogr, 57, 1571-1578. A quick solution:ab initiostructure determination of a 19 kDa metalloproteinase usingACORN. DOI:10.1107/s090744490101335x. PMID:11679721.
Catalytic Residues Roles
| Residue | Roles |
|---|---|
| Tyr106A | electrostatic stabiliser |
| Glu129A | electrostatic stabiliser |
| His128A | metal ligand |
| His132A | metal ligand |
| Asp143A | metal ligand |