PDBsum entry 1f8r

Oxidoreductase

PDB id: 1f8r

Contents

Protein chains

483 a.a. *

Ligands

NAG-NAG-FUC ×4

NAG ×4

CIT ×4

FAD ×4

Waters ×1869

* Residue conservation analysis

PDB id:

1f8r

Name:

Oxidoreductase

Title:

Crystal structure of l-amino acid oxidase from calloselasma rhodostoma complexed with citrate

Structure:

L-amino acid oxidase. Chain: a, b, c, d. Ec: 1.4.3.2

Source:

Calloselasma rhodostoma. Malayan pit viper. Organism_taxid: 8717. Secretion: venom

Biol. unit:

Dimer (from PQS)

Resolution:

2.00Å R-factor: 0.185 R-free: 0.210

Authors:

P.D.Pawelek,J.Cheah,R.Coulombe,P.Macheroux,S.Ghisla,A.Vrielink

Key ref:

P.D.Pawelek et al. (2000). The structure of L-amino acid oxidase reveals the substrate trajectory into an enantiomerically conserved active site. EMBO J, 19, 4204-4215. PubMed id: 10944103 DOI: 10.1093/emboj/19.16.4204

Date:

04-Jul-00 Release date: 24-Aug-00

Protein chains

P81382  (OXLA_CALRH) -  L-amino-acid oxidase from Calloselasma rhodostoma

Seq: 516 a.a.

Struc: 483 a.a.

Enzyme reactions

• Enzyme class: E.C.1.4.3.2 - L-amino-acid oxidase.
• Reaction: an L-alpha-amino acid + O2 + H2O = a 2-oxocarboxylate + H2O2 + NH4⁺
• Cofactor: FAD

FAD (Bound ligand (Het Group name = FAD) corresponds exactly)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1093/emboj/19.16.4204

EMBO J 19:4204-4215 (2000)

PubMed id: 10944103

The structure of L-amino acid oxidase reveals the substrate trajectory into an enantiomerically conserved active site.

P.D.Pawelek, J.Cheah, R.Coulombe, P.Macheroux, S.Ghisla, A.Vrielink.

ABSTRACT

The structure of L-amino acid oxidase (LAAO) from Calloselasma rhodostoma has been determined to 2.0 A resolution in the presence of two ligands: citrate and o-aminobenzoate (AB). The protomer consists of three domains: an FAD-binding domain, a substrate-binding domain and a helical domain. The interface between the substrate-binding and helical domains forms a 25 A long funnel, which provides access to the active site. Three AB molecules are visible within the funnel of the LAAO-AB complex; their orientations suggest the trajectory of the substrate to the active site. The innermost AB molecule makes hydrogen bond contacts with the active site residues, Arg90 and Gly464, and the aromatic portion of the ligand is situated in a hydrophobic pocket. These contacts are proposed to mimic those of the natural substrate. Comparison of LAAO with the structure of mammalian D-amino acid oxidase reveals significant differences in their modes of substrate entry. Furthermore, a mirror-symmetrical relationship between the two substrate-binding sites is observed which facilitates enantiomeric selectivity while preserving a common arrangement of the atoms involved in catalysis.

Selected figure(s)

Figure 2.
Figure 2 Stereoview of the LAAO–citrate complex in the region of (A) the FAD prosthetic group and (B) the citrate ligand. The protein main chain is shown as a green coil, and specific amino acid residues and the FAD molecule are depicted as ball-and-stick models with yellow and gray bonds, respectively. Water molecules are represented as red spheres. The hydrogen bond contacts are shown as black dashed lines.

Figure 4.
Figure 4 (A) Stereo view of the active sites of LAAO and porcine DAAO (pcDAAO) with the respective FAD cofactors superimposed along the isoalloxazine ring system. (B) Stereo view of the active sites of LAAO and the mirror-image pcDAAO with the AB ligands superimposed. Atoms and bonds are represented as capped sticks, with those corresponding to DAAO being shown in green and those from LAAO shown in red. The modeled His223 rotamer optimally situated to abstract a proton from the amino group from the substrate is shown in cyan. Superimposed AB molecules are shown in magenta. The mirror plane co-incident with the catalytic axis is shown in gray and those atoms involved in catalysis that lie along the mirror plane are enlarged. (C) Stereo representation of the modeled L-phenylalanine substrate within the active site. Amino acid residues, the FAD and L-phenylalanine molecules are shown in yellow, gray and cyan bonds, respectively. Hydrogen bonds are depicted as black dashed lines.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2000, 19, 4204-4215) copyright 2000.

Figures were selected by an automated process.