1sug
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Protein tyrosine phosphatase 1B (PTP1B) plays a key role as a negative | + | 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. |
==Disease== | ==Disease== | ||
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[[Category: Protein-tyrosine-phosphatase]] | [[Category: Protein-tyrosine-phosphatase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Iversen, L | + | [[Category: Iversen, L F.]] |
| - | [[Category: Kastrup, J | + | [[Category: Kastrup, J S.]] |
| - | [[Category: Moller, K | + | [[Category: Moller, K B.]] |
| - | [[Category: Pedersen, A | + | [[Category: Pedersen, A K.]] |
| - | [[Category: Peters, G | + | [[Category: Peters, G H.]] |
[[Category: GOL]] | [[Category: GOL]] | ||
[[Category: TRS]] | [[Category: TRS]] | ||
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[[Category: wpd-loop closed]] | [[Category: wpd-loop closed]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:05:20 2008'' |
Revision as of 13:05, 21 February 2008
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1.95 A structure of apo protein tyrosine phosphatase 1B
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[176885], Insulin resistance, susceptibility to OMIM:[176885]
About this Structure
1SUG is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Protein-tyrosine-phosphatase, with EC number 3.1.3.48 Full crystallographic information is available from OCA.
Reference
Water-molecule network and active-site flexibility of apo protein tyrosine phosphatase 1B., Pedersen AK, Peters G GH, Moller KB, Iversen LF, Kastrup JS, Acta Crystallogr D Biol Crystallogr. 2004 Sep;60(Pt 9):1527-34. Epub 2004, Aug 26. PMID:15333922
Page seeded by OCA on Thu Feb 21 15:05:20 2008
