1SUG

1.95 A structure of apo protein tyrosine phosphatase 1B

Summary for 1SUG

• Entry DOI: 10.2210/pdb1sug/pdb
• Related: 2hnp
• Descriptor: Protein-tyrosine phosphatase, non-receptor type 1, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, GLYCEROL, ... (4 entities in total)
• Functional Keywords: wpd-loop closed, water molecule network, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side: P18031
• Total number of polymer chains: 1
• Total formula weight: 37856.16

Authors

Pedersen, A.K.,Peters, G.H.,Moller, K.B.,Iversen, L.F.,Kastrup, J.S. (deposition date: 2004-03-26, release date: 2004-09-07, Last modification date: 2023-08-23)

Primary citation

Pedersen, A.K.,Peters G, G.H.,Moller, K.B.,Iversen, L.F.,Kastrup, J.S.
Water-molecule network and active-site flexibility of apo protein tyrosine phosphatase 1B.
Acta Crystallogr.,Sect.D, 60:1527-1534, 2004

PubMed Abstract: Protein tyrosine phosphatase 1B (PTP1B) plays a key role as a negative regulator of insulin and leptin signalling and is therefore considered to be an important molecular target for the treatment of type 2 diabetes and obesity. Detailed structural information about the structure of PTP1B, including the conformation and flexibility of active-site residues as well as the water-molecule network, is a key issue in understanding ligand binding and enzyme kinetics and in structure-based drug design. A 1.95 A apo PTP1B structure has been obtained, showing four highly coordinated water molecules in the active-site pocket of the enzyme; hence, the active site is highly solvated in the apo state. Three of the water molecules are located at positions that approximately correspond to the positions of the phosphate O atoms of the natural substrate phosphotyrosine and form a similar network of hydrogen bonds. The active-site WPD-loop was found to be in the closed conformation, in contrast to previous observations of wild-type PTPs in the apo state, in which the WPD-loop is open. The closed conformation is stabilized by a network of hydrogen bonds. These results provide new insights into and understanding of the active site of PTP1B and form a novel basis for structure-based inhibitor design.

PubMed: 15333922
DOI: 10.1107/S0907444904015094

Experimental method

X-RAY DIFFRACTION (1.95 Å)