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PDBsum entry 1f8r
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Oxidoreductase
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PDB id
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1f8r
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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The structure of l-Amino acid oxidase reveals the substrate trajectory into an enantiomerically conserved active site.
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Authors
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P.D.Pawelek,
J.Cheah,
R.Coulombe,
P.Macheroux,
S.Ghisla,
A.Vrielink.
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Ref.
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EMBO J, 2000,
19,
4204-4215.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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.
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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.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(2000,
19,
4204-4215)
copyright 2000.
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