PMID- 16806267 OWN - NLM STAT- MEDLINE DCOM- 20060926 LR - 20161124 IS - 0022-2836 (Print) IS - 0022-2836 (Linking) VI - 360 IP - 5 DP - 2006 Jul 28 TI - Crystal structure of the catalytic domain of human MAP kinase phosphatase 5: structural insight into constitutively active phosphatase. PG - 946-55 AB - MAP kinase phosphatase 5 (MKP5) is a member of the mitogen-activated protein kinase phosphatase (MKP) family and selectively dephosphorylates JNK and p38. We have determined the crystal structure of the catalytic domain of human MKP5 (MKP5-C) to 1.6 A. In previously reported MKP-C structures, the residues that constitute the active site are seriously deviated from the active conformation of protein tyrosine phosphatases (PTPs), which are accompanied by low catalytic activity. High activities of MKPs are achieved by binding their cognate substrates, representing substrate-induced activation. However, the MKP5-C structure adopts an active conformation of PTP even in the absence of its substrate binding, which is consistent with the previous results that MKP5 solely possesses the intrinsic activity. Further, we identify a sequence motif common to the members of MKPs having low catalytic activity by comparing structures and sequences of other MKPs. Our structural information provides an explanation of constitutive activity of MKP5 as well as the structural insight into substrate-induced activation occurred in other MKPs. FAU - Jeong, Dae Gwin AU - Jeong DG AD - Systemic Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 52 Eoeun-Dong, Yuseong-Gu, Daejeon, 305-333, Republic of Korea. FAU - Yoon, Tae-Sung AU - Yoon TS FAU - Kim, Jae Hoon AU - Kim JH FAU - Shim, Mi Young AU - Shim MY FAU - Jung, Suk-Kyeong AU - Jung SK FAU - Son, Jeong Hee AU - Son JH FAU - Ryu, Seong Eon AU - Ryu SE FAU - Kim, Seung Jun AU - Kim SJ LA - eng SI - PDB/1ZZW PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060609 PL - Netherlands TA - J Mol Biol JT - Journal of molecular biology JID - 2985088R RN - 0 (Intracellular Signaling Peptides and Proteins) RN - EC 3.1.3.16 (DUSP10 protein, human) RN - EC 3.1.3.16 (Mitogen-Activated Protein Kinase Phosphatases) RN - EC 3.1.3.48 (Dual-Specificity Phosphatases) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatases) SB - IM MH - Amino Acid Sequence MH - Catalysis MH - Catalytic Domain MH - Crystallography, X-Ray MH - Dual-Specificity Phosphatases MH - Humans MH - Intracellular Signaling Peptides and Proteins MH - Mitogen-Activated Protein Kinase Phosphatases MH - *Models, Molecular MH - Molecular Sequence Data MH - Protein Conformation MH - Protein Tyrosine Phosphatases/*chemistry MH - Sequence Homology, Amino Acid MH - Substrate Specificity EDAT- 2006/06/30 09:00 MHDA- 2006/09/27 09:00 CRDT- 2006/06/30 09:00 PHST- 2006/01/17 00:00 [received] PHST- 2006/04/26 00:00 [revised] PHST- 2006/05/23 00:00 [accepted] PHST- 2006/06/30 09:00 [pubmed] PHST- 2006/09/27 09:00 [medline] PHST- 2006/06/30 09:00 [entrez] AID - S0022-2836(06)00673-5 [pii] AID - 10.1016/j.jmb.2006.05.059 [doi] PST - ppublish SO - J Mol Biol. 2006 Jul 28;360(5):946-55. doi: 10.1016/j.jmb.2006.05.059. Epub 2006 Jun 9.