6QB6

Mcl1 in complex with a Fab

Summary for 6QB6

• Entry DOI: 10.2210/pdb6qb6/pdb
• Related: 6FS0 6QB3 6QB4
• Descriptor: Induced myeloid leukemia cell differentiation protein Mcl-1, Fab Heavy Chain, Fab Light Chain, ... (4 entities in total)
• Functional Keywords: mcl1, fab, azd5991, apoptosis
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 66210.77

Authors

Hargreaves, D. (deposition date: 2018-12-20, release date: 2019-11-06, Last modification date: 2024-10-16)

Primary citation

Luptak, J.,Bista, M.,Fisher, D.,Flavell, L.,Gao, N.,Wickson, K.,Kazmirski, S.L.,Howard, T.,Rawlins, P.B.,Hargreaves, D.
Antibody fragments structurally enable a drug-discovery campaign on the cancer target Mcl-1.
Acta Crystallogr D Struct Biol, 75:1003-1014, 2019

PubMed 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.

PubMed: 31692474
DOI: 10.1107/S2059798319014116

Experimental method

X-RAY DIFFRACTION (2.24 Å)