Dihydrodipicolinate reductase
Dihydrodipicolinate reductase catalyses the conversion of 4-hydroxy-tetrahydrodipicolinate (HTPA) to tetrahydrodipicolinate. It can use both NADH and NADPH as a reductant, with NADH being twice as effective as NADPH
The enzyme is a component of the biosynthetic pathway that leads to diaminopimelate and lysine in bacteria and higher plants. Because these pathways are unique to microorganisms and plants, they may represent attractive targets for new antimicrobial or herbicidal compounds.
Reference Protein and Structure
- Sequence
-
P04036
(1.17.1.8)
(Sequence Homologues)
(PDB Homologues)
- Biological species
-
Escherichia coli K-12 (Bacteria)
- PDB
-
1arz
- ESCHERICHIA COLI DIHYDRODIPICOLINATE REDUCTASE IN COMPLEX WITH NADH AND 2,6 PYRIDINE DICARBOXYLATE
(2.6 Å)
- Catalytic CATH Domains
-
3.30.360.10
(see all for 1arz)
Enzyme Reaction (EC:1.17.1.8)
+
+
→
+
+
Alternative enzyme names: Dihydrodipicolinic acid reductase, Dihydrodipicolinate reductase, DapB (gene name), 2,3,4,5-tetrahydrodipicolinate:NAD(P)(+) oxidoreductase,
Enzyme Mechanism
Introduction
Lysine polarises the imine to promote hydride transfer from NADH, and then stabilises the enemine intermediate. The intermediate then removes a proton from water, which is activated by histidine.
Catalytic Residues Roles
| UniProt | PDB* (1arz) | ||
| His159 | His159A | Acts as a general acid/base to activate a water molecule to protonate the intermediate. | activator, proton shuttle (general acid/base) |
| Lys163 | Lys163A | Polarises alpha,beta-unsaturated imine, stabilises enemine intermediate. | activator, proton shuttle (general acid/base), 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
- Scapin G et al. (1997), Biochemistry, 36, 15081-15088. Three-Dimensional Structure ofEscherichia coliDihydrodipicolinate Reductase in Complex with NADH and the Inhibitor 2,6-Pyridinedicarboxylate†,‡. DOI:10.1021/bi9719915. PMID:9398235.
Catalytic Residues Roles
| Residue | Roles |
|---|---|
| His159A | proton shuttle (general acid/base) |
| Lys163A | activator, proton shuttle (general acid/base) |
| His159A | activator |
| Lys163A | electrostatic stabiliser |