6RTR

Piperideine-6-carboxylate dehydrogenase from Streptomyces clavuligerus

Summary for 6RTR

• Entry DOI: 10.2210/pdb6rtr/pdb
• Related: 6RTS 6RTT 6RTU
• Descriptor: Semialdehyde dehydrogenase Pcd, SULFATE ION, GLYCEROL, ... (5 entities in total)
• Functional Keywords: oxidoreductase, antibiotic biosynthesis, streptomyces clavuligerus
• Biological source: Streptomyces clavuligerus ATCC 27064
• Total number of polymer chains: 2
• Total formula weight: 109492.00

Authors

Hasse, D.,Huelsemann, J.,Carlsson, G.,Andersson, I. (deposition date: 2019-05-26, release date: 2019-12-18, Last modification date: 2024-01-24)

Primary citation

Hasse, D.,Hulsemann, J.,Carlsson, G.H.,Valegard, K.,Andersson, I.
Structure and mechanism of piperideine-6-carboxylate dehydrogenase from Streptomyces clavuligerus.
Acta Crystallogr D Struct Biol, 75:1107-1118, 2019

PubMed Abstract: The core of β-lactam antibiotics originates from amino acids of primary metabolism in certain microorganisms. β-Lactam-producing bacteria, including Streptomyces clavuligerus, synthesize the precursor of the amino acid α-aminoadipic acid by the catabolism of lysine in two steps. The second reaction, the oxidation of piperideine-6-carboxylate (or its open-chain form α-aminoadipate semialdehyde) to α-aminoadipic acid, is catalysed by the NAD-dependent enzyme piperideine-6-carboxylate dehydrogenase (P6CDH). This structural study, focused on ligand binding and catalysis, presents structures of P6CDH from S. clavuligerus in its apo form and in complexes with the cofactor NAD, the product α-aminoadipic acid and a substrate analogue, picolinic acid. P6CDH adopts the common aldehyde dehydrogenase fold, consisting of NAD-binding, catalytic and oligomerization domains. The product binds in the oxyanion hole, close to the catalytic residue Cys299. Clear density is observed for the entire cofactor, including the nicotinamide riboside, in the binary complex. NAD binds in an extended conformation with its nicotinamide ring overlapping with the binding site of the carboxylate group of the product, implying that the conformation of the cofactor may change during catalysis. The binding site of the substrate analogue overlaps with that of the product, suggesting that the cyclic form of the substrate, piperideine-6-carboxylate, may be accepted as a substrate by the enzyme. The catalytic mechanism and the roles of individual residues are discussed in light of these results.

PubMed: 31793904
DOI: 10.1107/S2059798319014852

Experimental method

X-RAY DIFFRACTION (1.55 Å)