 |
PDBsum entry 3pcb
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
(+ 0 more)
200 a.a.
|
|
|
|
|
|
|
|
|
|
|
(+ 0 more)
233 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structures of competitive inhibitor complexes of protocatechuate 3,4-Dioxygenase: multiple exogenous ligand binding orientations within the active site.
|
|
|
Authors
|
|
A.M.Orville,
N.Elango,
J.D.Lipscomb,
D.H.Ohlendorf.
|
|
|
Ref.
|
|
Biochemistry, 1997,
36,
10039-10051.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Protocatechuate 3,4-dioxygenase (3,4-PCD) catalyzes the oxidative ring cleavage
of 3,4-dihydroxybenzoate to produce beta-carboxy-cis, cis-muconate. Crystal
structures of Pseudomonas putida3,4-PCD [quaternary structure of
(alphabetaFe3+)12] complexed with seven competitive inhibitors
[3-hydroxyphenylacetate (MHP), 4-hydroxyphenylacetate (PHP), 3-hydroxybenzoate
(MHB), 4-hydroxybenzoate (PHB), 3-fluoro-4-hydroxybenzoate (FHB),
3-chloro-4-hydroxybenzoate (CHB), and 3-iodo-4-hydroxybenzoate (IHB)] are
reported at 2.0-2.2 A resolution with R-factors of 0. 0.159-0.179. The
inhibitors bind in a narrow active site crevasse lined with residues that
provide a microenvironment that closely matches the chemical characteristics of
the inhibitors. This results in as little as 20% solvent-exposed surface area
for the higher-affinity inhibitors (PHB, CHB, and FHB). In uncomplexed 3,4-PCD,
the active site Fe3+ is bound at the bottom of the active site crevasse by four
endogenous ligands and a solvent molecule (Wat827). The orientations of the
endogenous ligands are relatively unperturbed in each inhibitor complex, but the
inhibitors themselves bind to or near the iron in a range of positions, all of
which perturb the position of Wat827. The three lowest-affinity inhibitors (MHP,
PHP, and IHB) yield distorted trigonal bipyramidal iron coordination geometry in
which the inhibitor C4-phenolate group displaces the solvent ligand. MHB binds
within the active site, but neither its C3-OH group nor the solvent molecule
binds to the iron. The C4-phenolate group of the three highest-affinity
inhibitors (PHB, CHB, and FHB) coordinates the Fe3+ adjacent to Wat827,
resulting in a shift in its position to yield a six-coordinate distorted
octahedral geometry. The range of inhibitor orientations may mimic the
mechanistically significant stages of substrate binding to 3, 4-PCD. The
structure of the final substrate complex is reported in the following paper
[Orville, A. M., Lipscomb, J. D., & Ohlendorf, D. H. (1997) Biochemistry 36,
10052-10066].
|
|
|
Secondary reference #1
|
|
|
Title
|
|
Structure of protocatechuate 3,4-Dioxygenase from pseudomonas aeruginosa at 2.15 a resolution.
|
|
|
Authors
|
|
D.H.Ohlendorf,
A.M.Orville,
J.D.Lipscomb.
|
|
|
Ref.
|
|
J Mol Biol, 1994,
244,
586-608.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Secondary reference #2
|
|
|
Title
|
|
Structure and assembly of protocatechuate 3,4-Dioxygenase.
|
|
|
Authors
|
|
D.H.Ohlendorf,
J.D.Lipscomb,
P.C.Weber.
|
|
|
Ref.
|
|
Nature, 1988,
336,
403-405.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Secondary reference #3
|
|
|
Title
|
|
Determination of the quaternary structure of protocatechuate 3,4-Dioxygenase from pseudomonas aeruginosa.
|
|
|
Authors
|
|
D.H.Ohlendorf,
P.C.Weber,
J.D.Lipscomb.
|
|
|
Ref.
|
|
J Mol Biol, 1987,
195,
225-227.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
