PDBsum entry 3ldp

Chaperone

PDB id: 3ldp

Contents

Protein chains

381 a.a. *

Ligands

3P1 ×2

Waters ×259

* Residue conservation analysis

PDB id:

3ldp

Name:

Chaperone

Title:

Crystal structure of human grp78 (70kda heat shock protein 5 / bip) atpase domain in complex with small molecule inhibitor

Structure:

78 kda glucose-regulated protein. Chain: a, b. Fragment: atpase domain (residues 26-407). Synonym: grp 78, heat shock 70 kda protein 5, immunoglobulin heavy chain-binding protein, bip, endoplasmic reticulum lumenal ca(2+)- binding protein grp78. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hspa5, grp78. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.20Å R-factor: 0.213 R-free: 0.298

Authors:

P.Dokurno,A.E.Surgenor,T.Shaw,A.T.Macias,A.J.Massey,D.S.Williamson

Key ref:

A.T.Macias et al. (2011). Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity. J Med Chem, 54, 4034-4041. PubMed id: 21526763

Date:

13-Jan-10 Release date: 26-Jan-11

Protein chains

P11021  (BIP_HUMAN) -  Endoplasmic reticulum chaperone BiP from Homo sapiens

Seq: 654 a.a.

Struc: 381 a.a.

Enzyme reactions

• Enzyme class: E.C.3.6.4.10 - non-chaperonin molecular chaperone ATPase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺

ATP + H2O = ADP (Bound ligand (Het Group name = 3P1) matches with 48.72% similarity) + phosphate + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

J Med Chem 54:4034-4041 (2011)

PubMed id: 21526763

Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.

A.T.Macias, D.S.Williamson, N.Allen, J.Borgognoni, A.Clay, Z.Daniels, P.Dokurno, M.J.Drysdale, G.L.Francis, C.J.Graham, R.Howes, N.Matassova, J.B.Murray, R.Parsons, T.Shaw, A.E.Surgenor, L.Terry, Y.Wang, M.Wood, A.J.Massey.

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.