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5MIM

Xray structure of human furin bound with the 2,5-dideoxystreptamine derived small molecule inhibitor 1n

Summary for 5MIM
Entry DOI10.2210/pdb5mim/pdb
DescriptorFurin, CALCIUM ION, SODIUM ION, ... (6 entities in total)
Functional Keywordsproprotein convertase, inhibitor, protease, complex, hydrolase
Biological sourceHomo sapiens (Human)
Cellular locationGolgi apparatus, trans-Golgi network membrane ; Single- pass type I membrane protein : P09958
Total number of polymer chains1
Total formula weight53811.61
Authors
Dahms, S.O.,Guan-Sheng, J.,Than, M.E. (deposition date: 2016-11-28, release date: 2017-05-10, Last modification date: 2024-11-20)
Primary citationDahms, S.O.,Jiao, G.S.,Than, M.E.
Structural Studies Revealed Active Site Distortions of Human Furin by a Small Molecule Inhibitor.
ACS Chem. Biol., 12:1211-1216, 2017
Cited by
PubMed Abstract: Proprotein convertases (PCs) represent highly selective serine proteases that activate their substrates upon proteolytic cleavage. Their inhibition is a promising strategy for the treatment of several pathologies including cancer, atherosclerosis, hypercholesterolaemia, and infectious diseases. Here, we present the first experimental complex of furin with a non-substrate-like small molecule inhibitor, and the X-ray structure of the enzyme complexed to the small molecule inhibitor 1 at 1.9 Å resolution. Two molecules of inhibitor 1 were found to interact with furin. One is anchored at the S4 pocket of the enzyme and interferes directly with the conformation and function of the catalytic triade; the other molecule shows weaker binding and interacts with a distant, less conserved region of furin. The observed binding modes represent a new inhibition strategy of furin and imply the possibility to attain specificity among the PCs providing an innovative starting point of structure guided inhibitor development for furin.
PubMed: 28402100
DOI: 10.1021/acschembio.6b01110
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.9 Å)
Structure validation

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