1sug

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{{STRUCTURE_1sug| PDB=1sug | SCENE= }}
{{STRUCTURE_1sug| PDB=1sug | SCENE= }}
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'''1.95 A structure of apo protein tyrosine phosphatase 1B'''
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===1.95 A structure of apo protein tyrosine phosphatase 1B===
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==Overview==
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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.
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The line below this paragraph, {{ABSTRACT_PUBMED_15333922}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 15333922 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15333922}}
==About this Structure==
==About this Structure==
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==Reference==
==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:[http://www.ncbi.nlm.nih.gov/pubmed/15333922 15333922]
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:[http://www.ncbi.nlm.nih.gov/pubmed/15333922 15333922]
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Crystal structure of human protein tyrosine phosphatase 1B., Barford D, Flint AJ, Tonks NK, Science. 1994 Mar 11;263(5152):1397-404. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8128219 8128219]
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Affinity purification of recombinant protein-tyrosine phosphatase 1B using a highly selective inhibitor., Pedersen AK, Branner S, Mortensen SB, Andersen HS, Klausen KM, Moller KB, Moller NP, Iversen LF, J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Jan 5;799(1):1-8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14659430 14659430]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein-tyrosine-phosphatase]]
[[Category: Protein-tyrosine-phosphatase]]
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[[Category: Water molecule network]]
[[Category: Water molecule network]]
[[Category: Wpd-loop closed]]
[[Category: Wpd-loop closed]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 09:08:52 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 20:39:26 2008''

Revision as of 17:39, 28 July 2008

Image:1sug.png

Template:STRUCTURE 1sug

1.95 A structure of apo protein tyrosine phosphatase 1B

Template:ABSTRACT PUBMED 15333922

About this Structure

1SUG is a Single protein structure of sequence from Homo sapiens. 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

Crystal structure of human protein tyrosine phosphatase 1B., Barford D, Flint AJ, Tonks NK, Science. 1994 Mar 11;263(5152):1397-404. PMID:8128219

Affinity purification of recombinant protein-tyrosine phosphatase 1B using a highly selective inhibitor., Pedersen AK, Branner S, Mortensen SB, Andersen HS, Klausen KM, Moller KB, Moller NP, Iversen LF, J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Jan 5;799(1):1-8. PMID:14659430

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