9ENN

L-amino acid oxidase 4 (HcLAAO4) from the fungus Hebeloma cylindrosporum in complex with N-epsilon-acetyl-L-lysine

Summary for 9ENN

• Entry DOI: 10.2210/pdb9enn/pdb
• Related: 9ENH 9ENI 9ENJ 9ENK 9ENL 9ENM
• Descriptor: L-amino acid oxidase 4, DIHYDROFLAVINE-ADENINE DINUCLEOTIDE, N(6)-ACETYLLYSINE, ... (7 entities in total)
• Functional Keywords: l-amino acid oxidase, fad, flavoprotein, oxidoreductase
• Biological source: Hebeloma cylindrosporum
• Total number of polymer chains: 4
• Total formula weight: 258446.30

Authors

Gilzer, D.,Koopmeiners, S.,Fischer von Mollard, G.,Niemann, H.H. (deposition date: 2024-03-13, release date: 2024-08-14, Last modification date: 2024-10-09)

Primary citation

Koopmeiners, S.,Gilzer, D.,Widmann, C.,Berelsmann, N.,Spross, J.,Niemann, H.H.,Fischer von Mollard, G.
Crystal structure and enzyme engineering of the broad substrate spectrum l-amino acid oxidase 4 from the fungus Hebeloma cylindrosporum.
Febs Lett., 598:2306-2320, 2024

PubMed Abstract: l-Amino acid oxidases (LAAOs) catalyze the oxidative deamination of l-amino acids to α-keto acids. Recombinant production of LAAOs with broad substrate spectrum remains a formidable challenge. We previously achieved this for the highly active and thermostable LAAO4 of Hebeloma cylindrosporum (HcLAAO4). Here, we crystallized a proteolytically truncated surface entropy reduction variant of HcLAAO4 and solved its structure in substrate-free form and in complex with diverse substrates. The ability to support the aliphatic portion of a substrate's side chain by an overall hydrophobic active site is responsible for the broad substrate spectrum of HcLAAO4, including l-amino acids with big aromatic, acidic and basic side chains. Based on the structural findings, we generated an E288H variant with increased activity toward pharmaceutical building blocks of high interest.

PubMed: 39152524
DOI: 10.1002/1873-3468.15002

Experimental method

X-RAY DIFFRACTION (1.8 Å)