2oud | pdb_00002oud
Crystal structure of the catalytic domain of human MKP5
Structural highlights
Function[DUS10_HUMAN] Protein phosphatase involved in the inactivation of MAP kinases. Has a specificity for the MAPK11/MAPK12/MAPK13/MAPK14 subfamily.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedMAP 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. Crystal structure of the MAP kinase binding domain and the catalytic domain of human MKP5.,Tao X, Tong L Protein Sci. 2007 May;16(5):880-6. Epub 2007 Mar 30. PMID:17400920[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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