View source for 1nny

[[Image:1nny.gif|left|200px]]<br /><applet load="1nny" size="350" color="white" frame="true" align="right" spinBox="true" 
caption="1nny, resolution 2.40&Aring;" />
'''Potent, Selective Protein Tyrosine Phosphatase 1B Inhibitor Compound 23 Using a Linked-Fragment Strategy'''<br />

==Overview==
Protein tyrosine phosphatase 1B (PTP1B) is an enzyme that downregulates the insulin receptor. Inhibition of PTP1B is expected to improve insulin action, and the design of small molecule PTP1B inhibitors to treat type II diabetes has received considerable attention. In this work, NMR-based screening identified a nonselective competitive inhibitor of PTP1B. A second site ligand was also identified by NMR-based screening and then linked to the catalytic site ligand by rational design. X-ray data confirmed that the inhibitor bound with the catalytic site in the native, "open" conformation. The final compound displayed excellent potency and good selectivity over many other phosphatases. The modular approach to drug design described in this work should be applicable for the design of potent and selective inhibitors of other therapeutically relevant protein tyrosine phosphatases.

==Disease==
Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176885 176885]], Insulin resistance, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176885 176885]]

==About this Structure==
1NNY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=515:'>515</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1NNY OCA]. 

==Reference==
Discovery of a potent, selective protein tyrosine phosphatase 1B inhibitor using a linked-fragment strategy., Szczepankiewicz BG, Liu G, Hajduk PJ, Abad-Zapatero C, Pei Z, Xin Z, Lubben TH, Trevillyan JM, Stashko MA, Ballaron SJ, Liang H, Huang F, Hutchins CW, Fesik SW, Jirousek MR, J Am Chem Soc. 2003 Apr 9;125(14):4087-96. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12670229 12670229]
[[Category: Homo sapiens]]
[[Category: Protein-tyrosine-phosphatase]]
[[Category: Single protein]]
[[Category: Abad-Zapatero, C.]]
[[Category: Ballaron, S J.]]
[[Category: Fesik, S W.]]
[[Category: Hajduk, P J.]]
[[Category: Huang, F.]]
[[Category: Hutchins, C W.]]
[[Category: Jirousek, M R.]]
[[Category: Liang, H.]]
[[Category: Liu, G.]]
[[Category: Lubben, T.]]
[[Category: Pei, Z.]]
[[Category: Stashko, M A.]]
[[Category: Szczepankiewicz, B G.]]
[[Category: Trevillyan, J M.]]
[[Category: Xin, Z.]]
[[Category: 515]]
[[Category: dual-site oxamic acid inhibitor bound to p-loop]]
[[Category: protein tyrosine phosphatase fold]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:08:06 2008''