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PDBsum entry 1l7o
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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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Structural characterization of the reaction pathway in phosphoserine phosphatase: crystallographic "snapshots" of intermediate states.
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Authors
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W.Wang,
H.S.Cho,
R.Kim,
J.Jancarik,
H.Yokota,
H.H.Nguyen,
I.V.Grigoriev,
D.E.Wemmer,
S.H.Kim.
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Ref.
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J Mol Biol, 2002,
319,
421-431.
[DOI no: ]
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PubMed id
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Abstract
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Phosphoserine phosphatase (PSP) is a member of a large class of enzymes that
catalyze phosphoester hydrolysis using a phosphoaspartate-enzyme intermediate.
PSP is a likely regulator of the steady-state d-serine level in the brain, which
is a critical co-agonist of the N-methyl-d-aspartate type of glutamate
receptors. Here, we present high-resolution (1.5-1.9 A) structures of PSP from
Methanococcus jannaschii, which define the open state prior to substrate
binding, the complex with phosphoserine substrate bound (with a D to N mutation
in the active site), and the complex with AlF3, a transition-state analog for
the phospho-transfer steps in the reaction. These structures, together with
those described for the BeF3- complex (mimicking the phospho-enzyme) and the
enzyme with phosphate product in the active site, provide a detailed structural
picture of the full reaction cycle. The structure of the apo state indicates
partial unfolding of the enzyme to allow substrate binding, with refolding in
the presence of substrate to provide specificity. Interdomain and active-site
conformational changes are identified. The structure with the transition state
analog bound indicates a "tight" intermediate. A striking structure
homology, with significant sequence conservation, among PSP, P-type ATPases and
response regulators suggests that the knowledge of the PSP reaction mechanism
from the structures determined will provide insights into the reaction
mechanisms of the other enzymes in this family.
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Figure 3.
Figure 3. PSP structure: (a) a ribbon diagram; (b) a
topology diagram.
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Figure 5.
Figure 5. Structural "snapshots" of the PSP reaction cycle
in the active site. (a) The PSP reaction cycle. (b) Structure
and models in the active site. (I) The apo-enzyme structure.
(II) The substrate, PLS, bound structure, using mutant D11N.
(III) The model of Ser bound transition state structural
analogue. A Ser molecule was modeled in the AlF[3]-PSP active
site. (IV) Phospho-aspartyl enzyme intermediate structural
analogue. The PSP+BeF[3]^ - complex. (V) The transition state
structural analogue. AlF[3]-PSP complex. (VI) The product, Pi,
bound structure.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2002,
319,
421-431)
copyright 2002.
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