1TQF

Crystal structure of human Beta secretase complexed with inhibitor

Summary for 1TQF

• Entry DOI: 10.2210/pdb1tqf/pdb
• Descriptor: Beta-secretase 1, 3-{2-[(5-AMINOPENTYL)AMINO]-2-OXOETHOXY}-5-({[1-(4-FLUOROPHENYL)ETHYL]AMINO}CARBONYL)PHENYL PHENYLMETHANESULFONATE (3 entities in total)
• Functional Keywords: aspartyl protease, bace, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P56817
• Total number of polymer chains: 1
• Total formula weight: 45694.41

Authors

Munshi, S.,Chen, Z.,Kuo, L. (deposition date: 2004-06-17, release date: 2004-11-09, Last modification date: 2024-10-16)

Primary citation

Coburn, C.A.,Stachel, S.J.,Li, Y.M.,Rush, D.M.,Steele, T.G.,Chen-Dodson, E.,Holloway, M.K.,Xu, M.,Huang, Q.,Lai, M.T.,DiMuzio, J.,Crouthamel, M.C.,Shi, X.P.,Sardana, V.,Chen, Z.,Munshi, S.,Kuo, L.,Makara, G.M.,Annis, D.A.,Tadikonda, P.K.,Nash, H.M.,Vacca, J.P.,Wang, T.
Identification of a small molecule nonpeptide active site beta-secretase inhibitor that displays a nontraditional binding mode for aspartyl proteases.
J.Med.Chem., 47:6117-6119, 2004

PubMed Abstract: A small molecule nonpeptide inhibitor of beta-secretase has been developed, and its binding has been defined through crystallographic determination of the enzyme-inhibitor complex. The molecule is shown to bind to the catalytic aspartate residues in an unprecedented manner in the field of aspartyl protease inhibition. Additionally, the complex reveals a heretofore unknown S(3) subpocket that is created by the inhibitor. This structure has served an important role in the design of newer beta-secretase inhibitors.

PubMed: 15566281
DOI: 10.1021/jm049388p

Experimental method

X-RAY DIFFRACTION (1.8 Å)