5TJX

Structure of human plasma kallikrein

Summary for 5TJX

• Entry DOI: 10.2210/pdb5tjx/pdb
• Descriptor: Plasma kallikrein, (8E)-3-amino-1-methyl-15-[(1H-pyrazol-1-yl)methyl]-7,10,11,12,24,25-hexahydro-6H,18H,23H-19,22-(metheno)pyrido[4,3-j][1,9,13,17,18]benzodioxatriazacyclohenicosin-23-one, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: plasma kallikrein, protease, serine, inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Secreted: P03952
• Total number of polymer chains: 1
• Total formula weight: 30144.87

Authors

Partridge, J.R.,Choy, R.M.,Li, Z. (deposition date: 2016-10-05, release date: 2016-12-21, Last modification date: 2024-10-23)

Primary citation

Li, Z.,Partridge, J.,Silva-Garcia, A.,Rademacher, P.,Betz, A.,Xu, Q.,Sham, H.,Hu, Y.,Shan, Y.,Liu, B.,Zhang, Y.,Shi, H.,Xu, Q.,Ma, X.,Zhang, L.
Structure-Guided Design of Novel, Potent, and Selective Macrocyclic Plasma Kallikrein Inhibitors.
ACS Med Chem Lett, 8:185-190, 2017

PubMed Abstract: A series of macrocyclic analogues were designed and synthesized based on the cocrystal structure of small molecule plasma kallikrein (pKal) inhibitor, , with the pKal protease domain. This led to the discovery of a potent macrocyclic pKal inhibitor , with an IC of 2 nM for one olefinic isomer and 42.3 nM for the other olefinic isomer.

PubMed: 28197309
DOI: 10.1021/acsmedchemlett.6b00384

Experimental method

X-RAY DIFFRACTION (1.408 Å)