5k22

Crystal structure of the complex between human PRL-2 phosphatase in reduced state and Bateman domain of human CNNM3Crystal structure of the complex between human PRL-2 phosphatase in reduced state and Bateman domain of human CNNM3

Structural highlights 5k22 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 5k23, 5k24, 5k25 Gene: PTP4A2, PRL2, PTPCAAX2, BM-008 (HUMAN), CNNM3, ACDP3 (HUMAN) Activity: Protein-tyrosine-phosphatase, with EC number 3.1.3.48 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [TP4A2_HUMAN] Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. Promotes tumors. Inhibits geranylgeranyl transferase type II activity by blocking the association between RABGGTA and RABGGTB. [CNNM3_HUMAN] Probable metal transporter. Publication Abstract from PubMed PRLs (phosphatases of regenerating liver) are frequently overexpressed in human cancers and are prognostic markers of poor survival. Despite their potential as therapeutic targets, their mechanism of action is not understood in part due to their weak enzymatic activity. Previous studies revealed that PRLs interact with CNNM ion transporters and prevent CNNM4-dependent Mg(2+) transport, which is important for energy metabolism and tumor progression. Here, we report that PRL-CNNM complex formation is regulated by the formation of phosphocysteine. We show that cysteine in the PRL catalytic site is endogenously phosphorylated as part of the catalytic cycle and that phosphocysteine levels change in response to Mg(2+) levels. Phosphorylation blocks PRL binding to CNNM Mg(2+) transporters, and mutations that block the PRL-CNNM interaction prevent regulation of Mg(2+) efflux in cultured cells. The crystal structure of the complex of PRL2 and the CBS-pair domain of the Mg(2+) transporter CNNM3 reveals the molecular basis for the interaction. The identification of phosphocysteine as a regulatory modification opens new perspectives for signaling by protein phosphatases. Phosphocysteine in the PRL-CNNM pathway mediates magnesium homeostasis.,Gulerez I, Funato Y, Wu H, Yang M, Kozlov G, Miki H, Gehring K EMBO Rep. 2016 Dec;17(12):1890-1900. doi: 10.15252/embr.201643393. Epub 2016 Nov , 17. PMID:27856537 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Tyrosine phosphatase

spinqualitylabelsall models 5k22, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image