Amine oxigenase is an enzyme which converts amines to aldehydes(eq.1). Mammalian amine oxidases are divided into two families, monoamine oxidases(MAOs) and copper amine oxidases(CuAOs). CuAOs contain a Cu and a quinone derivative oxidant, and regulate the connective tissue formation. On the other hand, MAOs contain a flavin cofactor and catalyze the oxidation of several neurotransmitters. Lysyl oxidase belongs to the CuAOs, and catalyzes oxidative deamination of lysine residues in collagens and elastins. Recent research reported that lysyl oxidase gene is a gastric tumor suppressor gene.
Eq. 1. Oxidizing amine to aldehyde.
The protein described here is Phichia pastoris lysyl oxidase(PPLO) homodimer. Each subunit contains three domains; D2, D3 and D4 domains (only E.coli lysyl oxidase has D1 on the N-terminal region of D2). Quinone and Cu binding site exist in the D4 domains. Cu binding seems to regulate the enzymatic activity, because it dramatically changes the position of quinone. The prominent feature of PPLO is two hydrophilic caves, “lake” and “funnel”, which are located near the quinine and Cu binding site (fig.1). Lake is formed in the interface of two D4 domains. Lake is assumed to be the pathway for the transport of small molecules and ions such as substrate O2, product H2O2 and product NH4. Another cave, funnel, is the substrate binding site which locates near the TPQ. The entry site of LLPO funnel is relatively larger than any other structurally characterized CuAOs. This structural property may reflect the broader substrate specificity of PPLO.
Fig. 1. Two caves around quinone and copper binding site: Lake and Funnel.
Protein Data Bank (PDB)
Duff, A.P. Cohen, A.E. Ellis, P.J. Kuchar, J.A. Langley, D.B. Shepard, E.M. Dooley, D.M. Freeman, H.C. Guss, J.M.; "The Crystal Structure of Pichia pastoris Lysyl Oxidase"; Biochemistry; (2003) 42:15148-15157 PubMed:14690425.
author: Daisuke Ino