5KQP
Crystal structure of Apo-form LMW-PTP
Summary for 5KQP
| Entry DOI | 10.2210/pdb5kqp/pdb |
| Related | 5KQG 5KQL 5KQM |
| Descriptor | Low molecular weight phosphotyrosine protein phosphatase (2 entities in total) |
| Functional Keywords | lmw-ptp, hydrolase |
| Biological source | Homo sapiens (Human) |
| Cellular location | Cytoplasm: P24666 |
| Total number of polymer chains | 1 |
| Total formula weight | 20236.88 |
| Authors | Wang, J.,Zhang, Z.-Y.,Yu, Z.-H. (deposition date: 2016-07-06, release date: 2016-10-12, Last modification date: 2023-10-04) |
| Primary citation | He, R.,Wang, J.,Yu, Z.H.,Zhang, R.Y.,Liu, S.,Wu, L.,Zhang, Z.Y. Inhibition of low molecular weight protein tyrosine phosphatase by an induced-fit mechanism. J.Med.Chem., 2016 Cited by PubMed Abstract: The low molecular weight protein tyrosine phosphatase (LMW-PTP) is a regulator of a number of signaling pathways and has been implicated as a potential target for oncology and diabetes/obesity. There is significant therapeutic interest in developing potent and selective inhibitors to control LMW-PTP activity. We report the discovery of a novel class of LMW-PTP inhibitors derived from sulfophenyl acetic amide (SPAA), some of which exhibit greater than 50-fold preference for LMW-PTP over a large panel of PTPs. X-ray crystallography reveals that binding of SPAA-based inhibitors induces a striking conformational change in the LMW-PTP active site, leading to the formation of a previously undisclosed hydrophobic pocket to accommodate the α-phenyl ring in the ligand. This induced-fit mechanism is likely a major contributor responsible for the exquisite inhibitor selectivity. PubMed: 27676368DOI: 10.1021/acs.jmedchem.6b00993 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.052 Å) |
Structure validation
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