1M3G

SOLUTION STRUCTURE OF THE CATALYTIC DOMAIN OF MAPK PHOSPHATASE PAC-1: INSIGHTS INTO SUBSTRATE-INDUCED ENZYMATIC ACTIVATION

Replaces:  1IKZ

Summary for 1M3G

• Entry DOI: 10.2210/pdb1m3g/pdb
• NMR Information: BMRB: 5552
• Descriptor: DUAL SPECIFICITY PROTEIN PHOSPHATASE 2 (1 entity in total)
• Functional Keywords: catalytic domain, mapk phosphatase, pac-1, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q05923
• Total number of polymer chains: 1
• Total formula weight: 16129.42

Authors

Farooq, A.,Zhou, M.-M. (deposition date: 2002-06-27, release date: 2003-06-27, Last modification date: 2024-05-22)

Primary citation

Farooq, A.,Plotnikova, O.,Chaturvedi, G.,Yan, S.,Zeng, L.,Zhang, Q.,Zhou, M.-M.
Solution Structure of the MAPK Phosphatase PAC-1 Catalytic Domain Insights into Substrate-Induced Enzymatic Activation of MKP
Structure, 11:155-164, 2003

PubMed Abstract: Inactivation of mitogen-activated protein kinases (MAPKs) by MAPK phosphatases (MKPs) is accomplished via substrate-induced activation of the latter enzymes; however, the structural basis for the underlying mechanism remains elusive. Here, we report the three-dimensional solution structure of the C-terminal phosphatase domain of the prototypical MKP PAC-1, determined when bound to phosphate. Structural and biochemical analyses reveal unique active site geometry of the enzyme important for binding to phosphorylated threonine and tyrosine of MAPK ERK2. Our study further demonstrates that the dynamic interaction between the N-terminal kinase binding domain and the C-terminal phosphatase domain of an MKP is directly coupled to MAPK-induced conformational change of the phosphatase active site, which is essential for eliciting its full enzymatic activity.

PubMed: 12575935
DOI: 10.1016/S0969-2126(02)00943-7

Experimental method

SOLUTION NMR