PDBsum entry 3eyl

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protein ligands metals Protein-protein interface(s) links
Ligase PDB id
Protein chains
101 a.a. *
SMK ×2
_ZN ×2
Waters ×3
* Residue conservation analysis
PDB id:
Name: Ligase
Title: Crystal structure of xiap bir3 domain in complex with a smac compound
Structure: Baculoviral iap repeat-containing protein 4. Chain: a, b. Fragment: unp residues 241-356. Synonym: e3 ubiquitin-protein ligase xiap, inhibitor of apo protein 3, x-linked inhibitor of apoptosis protein, x-linke iap-like protein, hilp. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: birc4, api3, iap3, xiap. Expressed in: escherichia coli. Expression_system_taxid: 562
3.00Å     R-factor:   0.191     R-free:   0.239
Authors: F.Cossu,M.Milani,E.Mastrangelo,M.Bolognesi
Key ref: F.Cossu et al. (2009). Designing Smac-mimetics as antagonists of XIAP, cIAP1, and cIAP2. Biochem Biophys Res Commun, 378, 162-167. PubMed id: 18992220 DOI: 10.1016/j.bbrc.2008.10.139
21-Oct-08     Release date:   25-Nov-08    
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Protein chains
Pfam   ArchSchema ?
P98170  (XIAP_HUMAN) -  E3 ubiquitin-protein ligase XIAP
497 a.a.
101 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain


DOI no: 10.1016/j.bbrc.2008.10.139 Biochem Biophys Res Commun 378:162-167 (2009)
PubMed id: 18992220  
Designing Smac-mimetics as antagonists of XIAP, cIAP1, and cIAP2.
F.Cossu, E.Mastrangelo, M.Milani, G.Sorrentino, D.Lecis, D.Delia, L.Manzoni, P.Seneci, C.Scolastico, M.Bolognesi.
Inhibitor of apoptosis proteins (IAPs) such as XIAP, cIAP1, and cIAP2 are upregulated in many cancer cells. Several compounds targeting IAPs and inducing cell death in cancer cells have been developed. Some of these are synthesized mimicking the N-terminal tetrapeptide sequence of Smac/DIABLO, the natural endogenous IAPs inhibitor. Starting from such conceptual design, we generated a library of 4-substituted azabicyclo[5.3.0]alkane Smac-mimetics. Here we report the crystal structure of the BIR3 domain from XIAP in complex with Smac037, a compound designed according to structural principles emerging from our previously analyzed XIAP BIR3/Smac-mimetic complexes. In parallel, we present an in silico docking analysis of three Smac-mimetics to the BIR3 domain of cIAP1, providing general considerations for the development of high affinity lead compounds targeting three members of the IAP family.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20734142 T.S.Griffith, T.A.Kucaba, M.A.O'Donnell, J.Burns, C.Benetatos, M.A.McKinlay, S.Condon, and S.Chunduru (2011).
Sensitization of human bladder tumor cells to TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis with a small molecule IAP antagonist.
  Apoptosis, 16, 13-26.  
20001744 A.K.Camara, E.J.Lesnefsky, and D.F.Stowe (2010).
Potential therapeutic benefits of strategies directed to mitochondria.
  Antioxid Redox Signal, 13, 279-347.  
20118959 D.Crommelin, P.Stolk, L.Besançon, V.Shah, K.Midha, and H.Leufkens (2010).
Pharmaceutical sciences in 2020.
  Nat Rev Drug Discov, 9, 99.  
20461078 D.Lecis, C.Drago, L.Manzoni, P.Seneci, C.Scolastico, E.Mastrangelo, M.Bolognesi, A.Anichini, H.Kashkar, H.Walczak, and D.Delia (2010).
Novel SMAC-mimetics synergistically stimulate melanoma cell death in combination with TRAIL and Bortezomib.
  Br J Cancer, 102, 1707-1716.  
20380038 E.J.Hennessy, A.E.Parker, and L.A.O'Neill (2010).
Targeting Toll-like receptors: emerging therapeutics?
  Nat Rev Drug Discov, 9, 293-307.  
20954235 F.Cossu, F.Malvezzi, G.Canevari, E.Mastrangelo, D.Lecis, D.Delia, P.Seneci, C.Scolastico, M.Bolognesi, and M.Milani (2010).
Recognition of Smac-mimetic compounds by the BIR domain of cIAP1.
  Protein Sci, 19, 2418-2429.
PDB codes: 3mup 3oz1
21204765 H.Zeng, S.Zhang, K.Y.Yang, T.Wang, J.L.Hu, L.L.Huang, and G.Wu (2010).
Knockdown of second mitochondria-derived activator of caspase expression by RNAi enhances growth and cisplatin resistance of human lung cancer cells.
  Cancer Biother Radiopharm, 25, 705-712.  
  19923725 M.D.Herman, M.Moche, S.Flodin, M.Welin, L.Trésaugues, I.Johansson, M.Nilsson, P.Nordlund, and T.Nyman (2009).
Structures of BIR domains from human NAIP and cIAP2.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 1091-1096.
PDB codes: 2uvl 2vm5
19407932 M.L.Tan, J.P.Ooi, N.Ismail, A.I.Moad, and T.S.Muhammad (2009).
Programmed cell death pathways and current antitumor targets.
  Pharm Res, 26, 1547-1560.  
19551381 P.Hersey, and X.D.Zhang (2009).
Treatment combinations targeting apoptosis to improve immunotherapy of melanoma.
  Cancer Immunol Immunother, 58, 1749-1759.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.