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PDBsum entry 2ouc
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the map kinase binding domain and the catalytic domain of human mkp5.
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Authors
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X.Tao,
L.Tong.
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Ref.
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Protein Sci, 2007,
16,
880-886.
[DOI no: ]
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PubMed id
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Abstract
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MAP kinase phosphatases (MKPs) have crucial roles in regulating the signaling
activity of MAP kinases and are potential targets for drug discovery against
human diseases. These enzymes contain a catalytic domain (CD) as well as a
binding domain (BD) that help recognize the target MAP kinase. We report here
the crystal structures at up to 2.2 A resolution of the BD and CD of human MKP5
and compare them to the known structures from other MKPs. Dramatic structural
differences are observed between the BD of MKP5 and that of MKP3 determined
previously by NMR. In particular, the cluster of positively charged residues
that is important for MAP kinase binding is located in completely different
positions in the two structures, with a distance of 25 A between them. Moreover,
this cluster is alpha-helical in MKP5, while it forms a loop followed by a
beta-strand in MKP3. These large structural differences could be associated with
the distinct substrate preferences of these phosphatases, but further studies
are needed to confirm this. The CD of MKP5 is observed in an active
conformation, and two loops in the active site have backbone shifts of up to 5 A
relative to the inactive CDs from other MKPs.
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Figure 2.
Figure 2. Structure of the MAP kinase binding domain of MKP5. (A) Schematic representation of the structure of the binding domain
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Figure 5.
Figure 5. Structural comparison between the catalytic domains of MKP5
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The above figures are
reprinted
by permission from the Protein Society:
Protein Sci
(2007,
16,
880-886)
copyright 2007.
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