Water-molecule network and active-site flexibility of apo protein tyrosine phosphatase 1B

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Standard

Water-molecule network and active-site flexibility of apo protein tyrosine phosphatase 1B. / Pedersen, Anja Kallesøe; Peters G, G üNther H; Møller, Karin B; Iversen, Lars F; Kastrup, Jette Sandholm Jensen.

In: Acta Crystallographica. Section D: Biological Crystallography, Vol. 60, No. Pt 9, 09.2004, p. 1527-34.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Pedersen, AK, Peters G, GÜNH, Møller, KB, Iversen, LF & Kastrup, JSJ 2004, 'Water-molecule network and active-site flexibility of apo protein tyrosine phosphatase 1B', Acta Crystallographica. Section D: Biological Crystallography, vol. 60, no. Pt 9, pp. 1527-34. https://doi.org/10.1107/S0907444904015094

APA

Pedersen, A. K., Peters G, G. ÜN. H., Møller, K. B., Iversen, L. F., & Kastrup, J. S. J. (2004). Water-molecule network and active-site flexibility of apo protein tyrosine phosphatase 1B. Acta Crystallographica. Section D: Biological Crystallography, 60(Pt 9), 1527-34. https://doi.org/10.1107/S0907444904015094

Vancouver

Pedersen AK, Peters G GÜNH, Møller KB, Iversen LF, Kastrup JSJ. Water-molecule network and active-site flexibility of apo protein tyrosine phosphatase 1B. Acta Crystallographica. Section D: Biological Crystallography. 2004 Sep;60(Pt 9):1527-34. https://doi.org/10.1107/S0907444904015094

Author

Pedersen, Anja Kallesøe ; Peters G, G üNther H ; Møller, Karin B ; Iversen, Lars F ; Kastrup, Jette Sandholm Jensen. / Water-molecule network and active-site flexibility of apo protein tyrosine phosphatase 1B. In: Acta Crystallographica. Section D: Biological Crystallography. 2004 ; Vol. 60, No. Pt 9. pp. 1527-34.

Bibtex

@article{b05cda6171834514853cb010cd1cceef,
title = "Water-molecule network and active-site flexibility of apo protein tyrosine phosphatase 1B",
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.",
keywords = "Binding Sites, Catalysis, Humans, Isoenzymes, Models, Molecular, Protein Conformation, Protein Tyrosine Phosphatase, Non-Receptor Type 1, Protein Tyrosine Phosphatases, Water, X-Ray Diffraction",
author = "Pedersen, {Anja Kalles{\o}e} and {Peters G}, {G {\"u}Nther H} and M{\o}ller, {Karin B} and Iversen, {Lars F} and Kastrup, {Jette Sandholm Jensen}",
year = "2004",
month = "9",
doi = "10.1107/S0907444904015094",
language = "English",
volume = "60",
pages = "1527--34",
journal = "Acta Crystallographica Section D: Structural Biology",
issn = "2059-7983",
publisher = "International Union of Crystallography",
number = "Pt 9",

}

RIS

TY - JOUR

T1 - Water-molecule network and active-site flexibility of apo protein tyrosine phosphatase 1B

AU - Pedersen, Anja Kallesøe

AU - Peters G, G üNther H

AU - Møller, Karin B

AU - Iversen, Lars F

AU - Kastrup, Jette Sandholm Jensen

PY - 2004/9

Y1 - 2004/9

N2 - 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.

AB - 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.

KW - Binding Sites

KW - Catalysis

KW - Humans

KW - Isoenzymes

KW - Models, Molecular

KW - Protein Conformation

KW - Protein Tyrosine Phosphatase, Non-Receptor Type 1

KW - Protein Tyrosine Phosphatases

KW - Water

KW - X-Ray Diffraction

U2 - 10.1107/S0907444904015094

DO - 10.1107/S0907444904015094

M3 - Journal article

C2 - 15333922

VL - 60

SP - 1527

EP - 1534

JO - Acta Crystallographica Section D: Structural Biology

JF - Acta Crystallographica Section D: Structural Biology

SN - 2059-7983

IS - Pt 9

ER -

ID: 44729794