6QFH

Crystal Structure of Human Kallikrein 6 (N217D/I218Y/K224R) in complex with GSK144.

6QFH の概要

• エントリーDOI: 10.2210/pdb6qfh/pdb
• 分子名称: Kallikrein-6, 4-[(5-phenyl-1~{H}-imidazol-2-yl)methylamino]-2-(pyridin-3-ylmethoxy)benzenecarboximidamide, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: protease, inhibitor, complex, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 49716.17

構造登録者

Thorpe, J.H. (登録日: 2019-01-10, 公開日: 2019-05-08, 最終更新日: 2024-10-16)

主引用文献

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

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: 31045568
DOI: 10.1107/S2053230X19003169

実験手法

X-RAY DIFFRACTION (1.65 Å)