3FZL

Crystal Structures of Hsc70/Bag1 in Complex with Small Molecule Inhibitors

Summary for 3FZL

• Entry DOI: 10.2210/pdb3fzl/pdb
• Related: 3FZF 3FZH 3FZK 3FZM
• Descriptor: Heat shock cognate 71 kDa protein, BAG family molecular chaperone regulator 1, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (5 entities in total)
• Functional Keywords: hsp70, hsc70, bag1, heat shock, chaperone, protein folding, adenosine, nucleotide, nucleotide exchange factor, small molecule inhibitor, atp-binding, nucleotide-binding, stress response, apoptosis
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm: P11142; Isoform 1: Nucleus. Isoform 2: Cytoplasm. Isoform 4: Cytoplasm: Q99933
• Total number of polymer chains: 2
• Total formula weight: 55922.26

Authors

Dokurno, P.,Williamson, D.S.,Murray, J.B.,Surgenor, A.E. (deposition date: 2009-01-26, release date: 2009-03-17, Last modification date: 2024-10-30)

Primary citation

Williamson, D.S.,Borgognoni, J.,Clay, A.,Daniels, Z.,Dokurno, P.,Drysdale, M.J.,Foloppe, N.,Francis, G.L.,Graham, C.J.,Howes, R.,Macias, A.T.,Murray, J.B.,Parsons, R.,Shaw, T.,Surgenor, A.E.,Terry, L.,Wang, Y.,Wood, M.,Massey, A.J.
Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design
J.Med.Chem., 52:1510-1513, 2009

PubMed Abstract: The design and synthesis of novel adenosine-derived inhibitors of HSP70, guided by modeling and X-ray crystallographic structures of these compounds in complex with HSC70/BAG-1, is described. Examples exhibited submicromolar affinity for HSP70, were highly selective over HSP90, and some displayed potency against HCT116 cells. Exposure of compound 12 to HCT116 cells caused significant reduction in cellular levels of Raf-1 and Her2 at concentrations similar to that which caused cell growth arrest.

PubMed: 19256508
DOI: 10.1021/jm801627a

Experimental method

X-RAY DIFFRACTION (2.2 Å)