2QBS
Crystal structure of ptp1b-inhibitor complex
Summary for 2QBS
| Entry DOI | 10.2210/pdb2qbs/pdb |
| Related | 2QBP 2QBQ 2QBR |
| Descriptor | Tyrosine-protein phosphatase non-receptor type 1, 4-BROMO-3-(CARBOXYMETHOXY)-5-[3-(CYCLOHEXYLAMINO)PHENYL]THIOPHENE-2-CARBOXYLIC ACID (3 entities in total) |
| Functional Keywords | protein-inhibitor complex, hydrolase |
| Biological source | Homo sapiens (human) |
| Cellular location | Endoplasmic reticulum membrane ; Peripheral membrane protein ; Cytoplasmic side : P18031 |
| Total number of polymer chains | 1 |
| Total formula weight | 35288.06 |
| Authors | |
| Primary citation | Wilson, D.P.,Wan, Z.K.,Xu, W.X.,Kirincich, S.J.,Follows, B.C.,Joseph-McCarthy, D.,Foreman, K.,Moretto, A.,Wu, J.,Zhu, M.,Binnun, E.,Zhang, Y.L.,Tam, M.,Erbe, D.V.,Tobin, J.,Xu, X.,Leung, L.,Shilling, A.,Tam, S.Y.,Mansour, T.S.,Lee, J. Structure-based optimization of protein tyrosine phosphatase 1B inhibitors: from the active site to the second phosphotyrosine binding site. J.Med.Chem., 50:4681-4698, 2007 Cited by PubMed Abstract: Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the insulin and leptin receptor pathways and thus an attractive therapeutic target for diabetes and obesity. Starting with a high micromolar lead compound, structure-based optimization of novel PTP1B inhibitors by extension of the molecule from the enzyme active site into the second phosphotyrosine binding site is described. Medicinal chemistry, guided by X-ray complex structure and molecular modeling, has yielded low nanomolar PTP1B inhibitors in an efficient manner. Compounds from this chemical series were found to be actively transported into hepatocytes. This active uptake into target tissues could be one of the possible avenues to overcome the poor membrane permeability of PTP1B inhibitors. PubMed: 17705360DOI: 10.1021/jm0702478 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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