9tpi | pdb_00009tpi
Survivin 1-122 in complex with a molecular tweezer-Histone-H3-peptide conjugate
Structural highlights
FunctionBIRC5_HUMAN Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis. Component of a chromosome passage protein complex (CPC) which is essential for chromosome alignment and segregation during mitosis and cytokinesis. Acts as an important regulator of the localization of this complex; directs CPC movement to different locations from the inner centromere during prometaphase to midbody during cytokinesis and participates in the organization of the center spindle by associating with polymerized microtubules. The complex with RAN plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules. May counteract a default induction of apoptosis in G2/M phase. The acetylated form represses STAT3 transactivation of target gene promoters. May play a role in neoplasia. Inhibitor of CASP3 and CASP7. Isoform 2 and isoform 3 do not appear to play vital roles in mitosis. Isoform 3 shows a marked reduction in its anti-apoptotic effects when compared with the displayed wild-type isoform.[1] [2] [3] [4] [5] [6] [7] [8] Publication Abstract from PubMedPeptide-modified supramolecular tweezers, a promising new class of chemical tools, were designed and employed to inhibit the interaction of the BIR domain of human survivin, a member of the chromosomal passenger complex (CPC), with the phosphorylated histone H3 N-terminal peptide. Fluorescence polarization measurements revealed a nanomolar affinity of the BIR domain for the peptide-tweezer, depending on the presence of lysine residue 121, as proven by the K121A mutant of survivin. Two crystal structures of C-terminally truncated human survivin with the peptide-tweezer molecules demonstrated that the peptide moiety binds the BIR domain as expected from the well-known published crystal structures of survivin with various peptides, but the tweezer itself, surprisingly, was bound to a putative Ca(2+) ion and the side chain of Pro26, corresponding to a previously unknown binding mode. Guided by the accessibility of survivin's lysine residues in the CPC, a number of new promising peptide tweezers was synthesized, able to connect both binding sites on the protein. Molecular tweezer-peptide conjugates disrupt the protein-protein interaction between survivin and histone H3 essential in mitosis.,Gsell C, Rebmann P, Opara K, Beuck C, Bayer P, Bier D, Vetter IR, Schrader T Beilstein J Org Chem. 2026 Mar 27;22:557-567. doi: 10.3762/bjoc.22.41. , eCollection 2026. PMID:41929663[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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