3LDP

Crystal structure of human GRP78 (70kDa heat shock protein 5 / BIP) ATPase domain in complex with small molecule inhibitor

Summary for 3LDP

• Entry DOI: 10.2210/pdb3ldp/pdb
• Related: 3LDL 3LDN 3LDO 3LDQ
• Descriptor: 78 kDa glucose-regulated protein, 8-[(quinolin-2-ylmethyl)amino]adenosine (3 entities in total)
• Functional Keywords: grp78, hsp70, hsc70, chaperone, heat shock, protein folding, atp-binding, adenosine, nucleoside, nucleotide-binding, stress response, small molecule inhibitor, selectivity, endoplasmic reticulum, phosphoprotein
• Biological source: Homo sapiens (human)
• Cellular location: Endoplasmic reticulum lumen: P11021
• Total number of polymer chains: 2
• Total formula weight: 85446.55

Authors

Dokurno, P.,Surgenor, A.E.,Shaw, T.,Macias, A.T.,Massey, A.J.,Williamson, D.S. (deposition date: 2010-01-13, release date: 2011-01-26, Last modification date: 2024-02-21)

Primary citation

Macias, A.T.,Williamson, D.S.,Allen, N.,Borgognoni, J.,Clay, A.,Daniels, Z.,Dokurno, P.,Drysdale, M.J.,Francis, G.L.,Graham, C.J.,Howes, R.,Matassova, N.,Murray, J.B.,Parsons, R.,Shaw, T.,Surgenor, A.E.,Terry, L.,Wang, Y.,Wood, M.,Massey, A.J.
Adenosine-Derived Inhibitors of 78 kDa Glucose Regulated Protein (Grp78) ATPase: Insights into Isoform Selectivity.
J.Med.Chem., 54:4034-4041, 2011

PubMed Abstract: 78 kDa glucose-regulated protein (Grp78) is a heat shock protein (HSP) involved in protein folding that plays a role in cancer cell proliferation. Binding of adenosine-derived inhibitors to Grp78 was characterized by surface plasmon resonance and isothermal titration calorimetry. The most potent compounds were 13 (VER-155008) with K(D) = 80 nM and 14 with K(D) = 60 nM. X-ray crystal structures of Grp78 bound to ATP, ADPnP, and adenosine derivative 10 revealed differences in the binding site between Grp78 and homologous proteins.

PubMed: 21526763
DOI: 10.1021/jm101625x

Experimental method

X-RAY DIFFRACTION (2.2 Å)