1bzh
From Proteopedia
(New page: 200px<br /> <applet load="1bzh" size="450" color="white" frame="true" align="right" spinBox="true" caption="1bzh, resolution 2.1Å" /> '''CYCLIC PEPTIDE INHIB...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1bzh. | + | [[Image:1bzh.jpg|left|200px]]<br /><applet load="1bzh" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1bzh" size=" | + | |
caption="1bzh, resolution 2.1Å" /> | caption="1bzh, resolution 2.1Å" /> | ||
'''CYCLIC PEPTIDE INHIBITOR OF HUMAN PTP1B'''<br /> | '''CYCLIC PEPTIDE INHIBITOR OF HUMAN PTP1B'''<br /> | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1BZH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] Full crystallographic information is available from [http:// | + | 1BZH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BZH OCA]. |
==Reference== | ==Reference== | ||
| Line 26: | Line 25: | ||
[[Category: tyrosine phosphatase]] | [[Category: tyrosine phosphatase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 15:33:55 2008'' |
Revision as of 13:33, 15 February 2008
|
CYCLIC PEPTIDE INHIBITOR OF HUMAN PTP1B
Contents |
Overview
Protein tyrosine phosphatases regulate diverse cellular processes and, represent important targets for therapeutic intervention in a number of, diseases. The crystal structures of protein tyrosine phosphatase 1B, (PTP1B) in complex with small molecule inhibitors based upon two classes, of phosphotyrosine mimetics, the (difluoronaphthylmethyl)phosphonic acids, and the fluoromalonyl tyrosines, have been determined to resolutions, greater than 2.3 A. The fluoromalonyl tyrosine residue was incorporated, within a cyclic hexapeptide modeled on an autophosphorylation site of the, epidermal growth factor receptor. The structure of this inhibitor bound to, PTP1B represents the first crystal structure of a, non-phosphonate-containing inhibitor and reveals the mechanism of, phosphotyrosine mimicry by the fluoromalonyl tyrosine residue and the, nature of its interactions within the catalytic site of PTP1B. In contrast, to complexes of PTP1B with phosphotyrosine-containing peptides, binding of, the fluoromalonyl tyrosine residue to the catalytic site of PTP1B is not, accompanied by closure of the catalytic site WPD loop. Structures of PTP1B, in complex with the (difluoronaphthylmethyl)phosphonic acid derivatives, reveal that substitutions of the naphthalene ring modulate the mode of, inhibitor binding to the catalytic site and provide the potential for, enhanced inhibitor affinity and the generation of PTP-specific inhibitors., These results provide a framework for the rational design of higher, affinity and more specific phosphotyrosine mimetic inhibitors of not only, protein tyrosine phosphatases but also SH2 and PTB domains.
Disease
Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[176885], Insulin resistance, susceptibility to OMIM:[176885]
About this Structure
1BZH is a Single protein structure of sequence from Homo sapiens. Active as Protein-tyrosine-phosphatase, with EC number 3.1.3.48 Full crystallographic information is available from OCA.
Reference
Structural basis for inhibition of the protein tyrosine phosphatase 1B by phosphotyrosine peptide mimetics., Groves MR, Yao ZJ, Roller PP, Burke TR Jr, Barford D, Biochemistry. 1998 Dec 22;37(51):17773-83. PMID:9922143
Page seeded by OCA on Fri Feb 15 15:33:55 2008
