6qb3
Apo Mcl1 in a complex with a scFv
Structural highlights
Function[MCL1_HUMAN] Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis.[1] Publication Abstract from PubMedApoptosis 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. Antibody fragments structurally enable a drug-discovery campaign on the cancer target Mcl-1.,Luptak J, Bista M, Fisher D, Flavell L, Gao N, Wickson K, Kazmirski SL, Howard T, Rawlins PB, Hargreaves D Acta Crystallogr D Struct Biol. 2019 Nov 1;75(Pt 11):1003-1014. doi:, 10.1107/S2059798319014116. Epub 2019 Oct 31. PMID:31692474[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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