PDBsum entry: 1zzw

Hydrolase

PDB id: 1zzw

Contents

Protein chains

147 a.a. *

Ligands

SO4 ×2

EDO

Waters ×263

* Residue conservation analysis

PDB id:

1zzw

Name:

Hydrolase

Title:

Crystal structure of catalytic domain of human map kinase phosphatase 5

Structure:

Dual specificity protein phosphatase 10. Chain: a, b. Fragment: catalytic domain. Synonym: mitogen-activated protein kinase phosphatase 5, map kinase phosphatase 5, mkp-5. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.60Å R-factor: 0.193 R-free: 0.217

Authors:

D.G.Jeong,T.S.Yoon,J.H.Kim,M.Y.Shim,S.K.Jeong,J.H.Son, S.E.Ryu,S.J.Kim

Key ref:

D.G.Jeong et al. (2006). Crystal structure of the catalytic domain of human MAP kinase phosphatase 5: structural insight into constitutively active phosphatase. J Mol Biol, 360, 946-955. PubMed id: 16806267 DOI: 10.1016/j.jmb.2006.05.059

Date:

14-Jun-05 Release date: 04-Jul-06

Protein chains

Q9Y6W6  (DUS10_HUMAN) -  Dual specificity protein phosphatase 10

Seq: 482 a.a.

Struc: 147 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 1: E.C.3.1.3.16 - Phosphoprotein phosphatase.
• Reaction: A phosphoprotein + H₂O = a protein + phosphate
• Enzyme class 2: E.C.3.1.3.48 - Protein-tyrosine-phosphatase.
• Reaction: Protein tyrosine phosphate + H₂O = protein tyrosine + phosphate

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Biological process: dephosphorylation (2 terms)
• Biochemical function: phosphatase activity (4 terms)

reference

DOI no: 10.1016/j.jmb.2006.05.059

J Mol Biol 360:946-955 (2006)

PubMed id: 16806267

Crystal structure of the catalytic domain of human MAP kinase phosphatase 5: structural insight into constitutively active phosphatase.

D.G.Jeong, T.S.Yoon, J.H.Kim, M.Y.Shim, S.K.Jung, J.H.Son, S.E.Ryu, S.J.Kim.

ABSTRACT

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.

Selected figure(s)

Figure 2.
Figure 2. (a) Cα trace. The Cα trace of the MKP5-C structure (thick line) is superimposed with that of the MKP3 structure (thin line). The regions of MKP5-C that cannot be aligned are colored green whereas the corresponding regions of MKP3 are colored red. The secondary structural elements are indicated. The point of view is the same as in Figure 1(a). (b) Comparison with MKP3. The active sites of MKP5-C (orange) and MKP3-C (grey) were superposed and presented as worm models. MKP5-C residues are labeled in black whereas MKP3-C residues (cyan) are labeled in red.

Figure 4.
Figure 4. (a) The superposition of the PTP loop, general acid loop and β3–β4 loop of MKP5-C (orange) with the equivalent regions of MKP3-C (grey). Selected side-chains of MKP5-C and MKP3-C are shown and labeled black and red, respectively. The hydrogen bond is represented as a dotted line. MKB is bound to the one side of inactive MKP-C, which include strand β3′, helices α2 and α5. The active structure is adapted from MKP5-C whereas the inactive one is from MKP3-C (PDB code: 1MKP). The regions that contributed to the binding to MKB are colored red. The PTP loop including its surrounding loops that adopt an active conformation are colored cyan whereas those that adopt an inactive one are in orange. (b) A hypothetical model of the substrate-induced activation by conformational rearrangement. MAPK binding to MKB allosterically induces a conformational transition of MKP-C from the β3′ strand to the β3–β4 loop. The transition may disrupt the interactions that stabilize the inactive conformation of MKP-C, which concomitantly lead to an active conformation.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2006, 360, 946-955) copyright 2006.

Figures were selected by an automated process.