PDBsum entry 6qb9

Apoptosis

PDB id: 6qb9

Contents

Protein chains

237 a.a.

Ligands

TLA ×2

Waters ×183

PDB id:

6qb9

Name:

Apoptosis

Title:

Structure of an anti-mcl1 scfv

Structure:

Scfv55. Chain: a, x. Engineered: yes

Source:

Homo sapiens. Organism_taxid: 9606. Expressed in: cricetulus griseus. Expression_system_taxid: 10029

Resolution:

1.85Å R-factor: 0.202 R-free: 0.239

Authors:

D.Hargreaves

Key ref:

J.Luptak et al. (2019). Antibody fragments structurally enable a drug-discovery campaign on the cancer target Mcl-1. Acta Crystallogr D Struct Biol, 75, 1003-1014. PubMed id: 31692474 DOI: 10.1107/S2059798319014116

Date:

20-Dec-18 Release date: 06-Nov-19

Protein chains

No UniProt id for this chain

Struc: 237 a.a.

DOI no: 10.1107/S2059798319014116

Acta Crystallogr D Struct Biol 75:1003-1014 (2019)

PubMed id: 31692474

Antibody fragments structurally enable a drug-discovery campaign on the cancer target Mcl-1.

J.Luptak, M.Bista, D.Fisher, L.Flavell, N.Gao, K.Wickson, S.L.Kazmirski, T.Howard, P.B.Rawlins, D.Hargreaves.

ABSTRACT

Apoptosis is a crucial process by which multicellular organisms control tissue growth, removal and inflammation. Disruption of the normal apoptotic function is often observed in cancer, where cell death is avoided by the overexpression of anti-apoptotic proteins of the Bcl-2 (B-cell lymphoma 2) family, including Mcl-1 (myeloid cell leukaemia 1). This makes Mcl-1 a potential target for drug therapy, through which normal apoptosis may be restored by inhibiting the protective function of Mcl-1. Here, the discovery and biophysical properties of an anti-Mcl-1 antibody fragment are described and the utility of both the scFv and Fab are demonstrated in generating an Mcl-1 crystal system amenable to iterative structure-guided drug design.