2B49

Crystal Structure of the Catalytic Domain of Protein Tyrosine Phosphatase, non-receptor Type 3

Summary for 2B49

• Entry DOI: 10.2210/pdb2b49/pdb
• Related: 1L8K
• Descriptor: protein tyrosine phosphatase, non-receptor type 3 (2 entities in total)
• Functional Keywords: protein tyrosine phosphatase, non-receptor type, human, structural genomics, structural genomics consortium, sgc, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Peripheral membrane protein; Cytoplasmic side: P26045
• Total number of polymer chains: 1
• Total formula weight: 32747.46

Authors

Ugochukwu, E.,Arrowsmith, C.,Barr, A.,Bunkoczi, G.,Das, S.,Debreczeni, J.,Edwards, A.,Eswaran, J.,Knapp, S.,Sundstrom, M.,Turnbull, A.,von Delft, F.,Weigelt, J.,Structural Genomics Consortium (SGC) (deposition date: 2005-09-23, release date: 2005-10-04, Last modification date: 2023-08-23)

Primary citation

Barr, A.J.,Ugochukwu, E.,Lee, W.H.,King, O.N.,Filippakopoulos, P.,Alfano, I.,Savitsky, P.,Burgess-Brown, N.A.,Muller, S.,Knapp, S.
Large-scale structural analysis of the classical human protein tyrosine phosphatome.
Cell(Cambridge,Mass.), 136:352-363, 2009

PubMed Abstract: Protein tyrosine phosphatases (PTPs) play a critical role in regulating cellular functions by selectively dephosphorylating their substrates. Here we present 22 human PTP crystal structures that, together with prior structural knowledge, enable a comprehensive analysis of the classical PTP family. Despite their largely conserved fold, surface properties of PTPs are strikingly diverse. A potential secondary substrate-binding pocket is frequently found in phosphatases, and this has implications for both substrate recognition and development of selective inhibitors. Structural comparison identified four diverse catalytic loop (WPD) conformations and suggested a mechanism for loop closure. Enzymatic assays revealed vast differences in PTP catalytic activity and identified PTPD1, PTPD2, and HDPTP as catalytically inert protein phosphatases. We propose a "head-to-toe" dimerization model for RPTPgamma/zeta that is distinct from the "inhibitory wedge" model and that provides a molecular basis for inhibitory regulation. This phosphatome resource gives an expanded insight into intrafamily PTP diversity, catalytic activity, substrate recognition, and autoregulatory self-association.

PubMed: 19167335
DOI: 10.1016/j.cell.2008.11.038

Experimental method

X-RAY DIFFRACTION (1.54 Å)