PDBsum entry: 2vm5

Apoptosis

PDB id: 2vm5

Contents

Protein chain

103 a.a. *

Ligands

GOL

Metals

_ZN

Waters ×51

* Residue conservation analysis

PDB id:

2vm5

Name:

Apoptosis

Title:

Human bir2 domain of baculoviral inhibitor of apoptosis repeat-containing 1 (birc1)

Structure:

Baculoviral iap repeat-containing protein 1. Chain: a. Fragment: bir2 domain, residues 141-244. Synonym: baculoviral inhibitor of apoptosis repeat-containing 1, neuronal apoptosis inhibitory protein. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.80Å R-factor: 0.181 R-free: 0.220

Authors:

M.D.Herman,M.Welin,C.H.Arrowsmith,H.Berglund,R.D.Busam, R.Collins,L.G.Dahlgren,A.M.Edwards,S.Flodin,A.Flores, S.Graslund,M.Hammarstrom,I.Johansson,A.Kallas,T.Karlberg, T.Kotenyova,L.Lehtio,M.Moche,M.E.Nilsson,T.Nyman,C.Persson, J.Sagemark,L.Svensson,A.G.Thorsell,L.Tresaugues, S.Van Den Berg,J.Weigelt,P.Nordlund, Structural Genomics Consortium (Sgc)

Key ref:

M.D.Herman et al. (2009). Structures of BIR domains from human NAIP and cIAP2. Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 1091-1096. PubMed id: 19923725

Date:

23-Jan-08 Release date: 29-Jan-08

Protein chain

Q13075  (BIRC1_HUMAN) -  Baculoviral IAP repeat-containing protein 1

Seq: 1403 a.a.

Struc: 103 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 

• Cellular component: intracellular (1 term)

Acta Crystallogr Sect F Struct Biol Cryst Commun 65:1091-1096 (2009)

PubMed id: 19923725

Structures of BIR domains from human NAIP and cIAP2.

M.D.Herman, M.Moche, S.Flodin, M.Welin, L.Trésaugues, I.Johansson, M.Nilsson, P.Nordlund, T.Nyman.

ABSTRACT

The inhibitor of apoptosis (IAP) family of proteins contains key modulators of apoptosis and inflammation that interact with caspases through baculovirus IAP-repeat (BIR) domains. Overexpression of IAP proteins frequently occurs in cancer cells, thus counteracting the activated apoptotic program. The IAP proteins have therefore emerged as promising targets for cancer therapy. In this work, X-ray crystallography was used to determine the first structures of BIR domains from human NAIP and cIAP2. Both structures harbour an N-terminal tetrapeptide in the conserved peptide-binding groove. The structures reveal that these two proteins bind the tetrapeptides in a similar mode as do other BIR domains. Detailed interactions are described for the P1'-P4' side chains of the peptide, providing a structural basis for peptide-specific recognition. An arginine side chain in the P3' position reveals favourable interactions with its hydrophobic moiety in the binding pocket, while hydrophobic residues in the P2' and P4' pockets make similar interactions to those seen in other BIR domain-peptide complexes. The structures also reveal how a serine in the P1' position is accommodated in the binding pockets of NAIP and cIAP2. In addition to shedding light on the specificity determinants of these two proteins, the structures should now also provide a framework for future structure-based work targeting these proteins.