6CWU

Protein Tyrosine Phosphatase 1B F135Y mutant

Summary for 6CWU

• Entry DOI: 10.2210/pdb6cwu/pdb
• Descriptor: Tyrosine-protein phosphatase non-receptor type 1, MAGNESIUM ION (3 entities in total)
• Functional Keywords: insulin signaling, diabetes, cancer, signaling, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 38477.08

Authors

Hjortness, M.,Zwart, P.,Sankaran, B.,Fox, J.M. (deposition date: 2018-03-31, release date: 2018-10-31, Last modification date: 2023-10-04)

Primary citation

Hjortness, M.K.,Riccardi, L.,Hongdusit, A.,Zwart, P.H.,Sankaran, B.,De Vivo, M.,Fox, J.M.
Evolutionarily Conserved Allosteric Communication in Protein Tyrosine Phosphatases.
Biochemistry, 57:6443-6451, 2018

PubMed Abstract: Protein tyrosine phosphatases (PTPs) are an important class of regulatory enzymes that exhibit aberrant activities in a wide range of diseases. A detailed mapping of allosteric communication in these enzymes could, thus, reveal the structural basis of physiologically relevant-and, perhaps, therapeutically informative-perturbations (i.e., mutations, post-translational modifications, or binding events) that influence their catalytic states. This study combines detailed biophysical studies of protein tyrosine phosphatase 1B (PTP1B) with bioinformatic analyses of the PTP family to examine allosteric communication in this class of enzymes. Results of X-ray crystallography, molecular dynamics simulations, and sequence-based statistical analyses indicate that PTP1B possesses a broadly distributed allosteric network that is evolutionarily conserved across the PTP family, and findings from both kinetic studies and mutational analyses show that this network is functionally intact in sequence-diverse PTPs. The allosteric network resolved in this study reveals new sites for targeting allosteric inhibitors of PTPs and helps explain the functional influence of a diverse set of disease-associated mutations.

PubMed: 30289703
DOI: 10.1021/acs.biochem.8b00656

Experimental method

X-RAY DIFFRACTION (2.08 Å)