6QFE
Crystal Structure of Human Kallikrein 5 in complex with GSK144
Summary for 6QFE
| Entry DOI | 10.2210/pdb6qfe/pdb |
| Descriptor | Kallikrein-5, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total) |
| Functional Keywords | protease, inhibitor, complex, hydrolase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 52519.96 |
| Authors | Thorpe, J.H. (deposition date: 2019-01-10, release date: 2019-05-08, Last modification date: 2024-11-13) |
| Primary citation | Thorpe, J.H.,Edgar, E.V.,Smith, K.J.,Lewell, X.Q.,Rella, M.,White, G.V.,Polyakova, O.,Nassau, P.,Walker, A.L.,Holmes, D.S.,Pearce, A.C.,Wang, Y.,Liddle, J.,Hovnanian, A. Evaluation of a crystallographic surrogate for kallikrein 5 in the discovery of novel inhibitors for Netherton syndrome. Acta Crystallogr.,Sect.F, 75:385-391, 2019 Cited by PubMed Abstract: The inhibition of kallikrein 5 (KLK5) has been identified as a potential strategy for treatment of the genetic skin disorder Netherton syndrome, in which loss-of-function mutations in the SPINK5 gene lead to down-regulation of the endogenous inhibitor LEKTI-1 and profound skin-barrier defects with severe allergic manifestations. To aid in the development of a medicine for this target, an X-ray crystallographic system was developed to facilitate fragment-guided chemistry and knowledge-based drug-discovery approaches. Here, the development of a surrogate crystallographic system in place of KLK5, which proved to be challenging to crystallize, is described. The biochemical robustness of the crystallographic surrogate and the suitability of the system for the study of small nonpeptidic fragments and lead-like molecules are demonstrated. PubMed: 31045568DOI: 10.1107/S2053230X19003169 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.67 Å) |
Structure validation
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