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PDBsum entry 1wkv
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References listed in PDB file
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Key reference
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Title
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Three-Dimensional structure of a new enzyme, O-Phosphoserine sulfhydrylase, Involved in l-Cysteine biosynthesis by a hyperthermophilic archaeon, Aeropyrum pernix k1, At 2.0a resolution.
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Authors
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Y.Oda,
K.Mino,
K.Ishikawa,
M.Ataka.
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Ref.
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J Mol Biol, 2005,
351,
334-344.
[DOI no: ]
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PubMed id
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Abstract
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O-Phosphoserine sulfhydrylase is a new enzyme found in a hyperthermophilic
archaeon, Aeropyrum pernix K1. This enzyme catalyzes a novel cysteine synthetic
reaction from O-phospho-l-serine and sulfide. The crystal structure of the
enzyme was determined at 2.0A resolution using the method of multi-wavelength
anomalous dispersion. A monomer consists of three domains, including an
N-terminal domain with a new alpha/beta fold. The topology folds of the middle
and C-terminal domains were similar to those of the O-acetylserine
sulfhydrylase-A from Salmonella typhimurium and the cystathionine beta-synthase
from human. The cofactor, pyridoxal 5'-phosphate, is bound in a cleft between
the middle and C-terminal domains through a covalent linkage to Lys127. Based on
the structure determined, O-phospho-l-serine could be rationally modeled into
the active site of the enzyme. An enzyme-substrate complex model and a mutation
experiment revealed that Arg297, unique to hyperthermophilic archaea, is one of
the most crucial residues for O-phosphoserine sulfhydrylation activity. There
are more hydrophobic areas and less electric charges at the dimer interface,
compared to the S.typhimurium O-acetylserine sulfhydrylase.
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Figure 2.
Figure 2. A detailed structure of the active site of OPSS.
(a) Stereo view of the active site region of OPSS. The cofactor
PLP and the bound acetate ion are located at the center of the
active site. Their 2F[o] -F[c] electron density is shown at 2s.
Hydrogen bonds are shown as broken lines. A Schiff base linkage
is shown as a thick, broken blue line. (b) A schematic of
hydrogen bond interactions among PLP moiety, protein and water
molecules. (c) Stereo view of a proposed model of the OPSS
active site with phosphoserine. Phosphoserine was built into the
active site to make a Schiff base linkage with PLP and to bind
with Thr152, Ser153, and Gln224. The negative charge of the
phosphate group of phosphoserine is presumably interacting with
Arg297. The Figure was produced with MOLSCRIPT.29
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Figure 4.
Figure 4. Stereo views of comparisons of the active site
regions between OPSS and S. typhimurium OASS or human CBS. (a) A
superposition of OPSS (green) and the mutant OASS bound with
methionine (gray). (b) A superposition of OPSS (green) and the
free form of wild-type OASS (gray). (c) A superposition of OPSS
(green) and CBS (gray). In CBS, a residue corresponding to
Thr203 of OPSS is not visible in its crystallographic structure.
The Figure was produced with MOLSCRIPT29 and Raster3D.30
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2005,
351,
334-344)
copyright 2005.
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