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PDBsum entry 5j89
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Immune system
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PDB id
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5j89
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References listed in PDB file
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Key reference
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Title
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Structural basis for small molecule targeting of the programmed death ligand 1 (pd-L1).
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Authors
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K.M.Zak,
P.Grudnik,
K.Guzik,
B.J.Zieba,
B.Musielak,
A.Dömling,
G.Dubin,
T.A.Holak.
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Ref.
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Oncotarget, 2016,
7,
30323-30335.
[DOI no: ]
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PubMed id
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Abstract
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Targeting the PD-1/PD-L1 immunologic checkpoint with monoclonal antibodies has
provided unprecedented results in cancer treatment in the recent years.
Development of chemical inhibitors for this pathway lags the antibody
development because of insufficient structural information. The first
nonpeptidic chemical inhibitors that target the PD-1/PD-L1 interaction have only
been recently disclosed by Bristol-Myers Squibb. Here, we show that these
small-molecule compounds bind directly to PD-L1 and that they potently block
PD-1 binding. Structural studies reveal a dimeric protein complex with a single
small molecule which stabilizes the dimer thus occluding the PD-1 interaction
surface of PD-L1s. The small-molecule interaction "hot spots" on PD-L1
surfaces suggest approaches for the PD-1/PD-L1 antagonist drug discovery.
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