PDBsum entry 1d6e

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Immune system/peptide inhibitor PDB id
Protein chains
177 a.a. *
179 a.a. *
225 a.a. *
Waters ×38
* Residue conservation analysis
PDB id:
Name: Immune system/peptide inhibitor
Title: Crystal structure of hla-dr4 complex with peptidomimetic and
Structure: Hla class ii histocompatibility antigen. Chain: a. Fragment: dr alpha chain, extracellular domain. Synonym: hla-dr4. Engineered: yes. Hla class ii histocompatibility antigen. Chain: b. Fragment: dr-4 beta chain, extracellular domain. Synonym: hla-dr4.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227. Staphylococcus aureus. Organism_taxid: 1280. Synthetic: yes. Other_details: the peptide was chemically synthesized.
Biol. unit: Tetramer (from PQS)
2.45Å     R-factor:   0.198     R-free:   0.226
Authors: A.Swain,R.Crowther,U.Kammlott
Key ref: D.R.Bolin et al. (2000). Peptide and peptide mimetic inhibitors of antigen presentation by HLA-DR class II MHC molecules. Design, structure-activity relationships, and X-ray crystal structures. J Med Chem, 43, 2135-2148. PubMed id: 10841792 DOI: 10.1021/jm000034h
13-Oct-99     Release date:   28-Jun-00    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P01903  (DRA_HUMAN) -  HLA class II histocompatibility antigen, DR alpha chain
254 a.a.
177 a.a.
Protein chain
Pfam   ArchSchema ?
P13760  (2B14_HUMAN) -  HLA class II histocompatibility antigen, DRB1-4 beta chain
266 a.a.
179 a.a.
Protein chain
Pfam   ArchSchema ?
P01552  (ETXB_STAAU) -  Enterotoxin type B
266 a.a.
225 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   3 terms 
  Biological process     immune response   3 terms 


DOI no: 10.1021/jm000034h J Med Chem 43:2135-2148 (2000)
PubMed id: 10841792  
Peptide and peptide mimetic inhibitors of antigen presentation by HLA-DR class II MHC molecules. Design, structure-activity relationships, and X-ray crystal structures.
D.R.Bolin, A.L.Swain, R.Sarabu, S.J.Berthel, P.Gillespie, N.J.Huby, R.Makofske, L.Orzechowski, A.Perrotta, K.Toth, J.P.Cooper, N.Jiang, F.Falcioni, R.Campbell, D.Cox, D.Gaizband, C.J.Belunis, D.Vidovic, K.Ito, R.Crowther, U.Kammlott, X.Zhang, R.Palermo, D.Weber, J.Guenot, Z.Nagy, G.L.Olson.
Molecular features of ligand binding to MHC class II HLA-DR molecules have been elucidated through a combination of peptide structure-activity studies and structure-based drug design, resulting in analogues with nanomolar affinity in binding assays. Stabilization of lead compounds against cathepsin B cleavage by N-methylation of noncritical backbone NH groups or by dipeptide mimetic substitutions has generated analogues that compete effectively against protein antigens in cellular assays, resulting in inhibition of T-cell proliferation. Crystal structures of four ternary complexes of different peptide mimetics with the rheumatoid arthritis-linked MHC DRB10401 and the bacterial superantigen SEB have been obtained. Peptide-sugar hybrids have also been identified using a structure-based design approach in which the sugar residue replaces a dipeptide. These studies illustrate the complementary roles played by phage display library methods, peptide analogue SAR, peptide mimetics substitutions, and structure-based drug design in the discovery of inhibitors of antigen presentation by MHC class II HLA-DR molecules.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20181657 S.Yanaka, M.Kudou, Y.Tanaka, T.Sasaki, S.Takemoto, A.Sakata, Y.Hattori, T.Koshi, S.Futaki, K.Tsumoto, and T.Nakashima (2010).
Contribution of the flexible loop region to the function of staphylococcal enterotoxin B.
  Protein Eng Des Sel, 23, 415-421.
PDB code: 3gp7
20503254 T.Burster, and B.O.Boehm (2010).
Processing and presentation of (pro)-insulin in the MHC class II pathway: the generation of antigen-based immunomodulators in the context of type 1 diabetes mellitus.
  Diabetes Metab Res Rev, 26, 227-238.  
19334714 P.K.Mandal, D.Limbrick, D.R.Coleman, G.A.Dyer, Z.Ren, J.S.Birtwistle, C.Xiong, X.Chen, J.M.Briggs, and J.S.McMurray (2009).
Conformationally constrained peptidomimetic inhibitors of signal transducer and activator of transcription. 3: Evaluation and molecular modeling.
  J Med Chem, 52, 2429-2442.  
18545669 C.A.Painter, A.Cruz, G.E.López, L.J.Stern, and Z.Zavala-Ruiz (2008).
Model for the peptide-free conformation of class II MHC proteins.
  PLoS ONE, 3, e2403.  
18809686 J.M.Fletcher, C.J.Morton, R.A.Zwar, S.S.Murray, P.D.O'Leary, and R.A.Hughes (2008).
Design of a Conformationally Defined and Proteolytically Stable Circular Mimetic of Brain-derived Neurotrophic Factor.
  J Biol Chem, 283, 33375-33383.  
17803448 H.Albrecht, M.Cosman, M.Ngu-Schwemlein, M.Corzett, K.W.Curran, C.Dolan, X.Fang, S.J.DeNardo, G.L.DeNardo, and R.Balhorn (2007).
Recombinant expression of the beta-subunit of HLA-DR10 for the selection of novel lymphoma targeting molecules.
  Cancer Biother Radiopharm, 22, 531-542.  
17681795 J.Xia, E.Bergseng, B.Fleckenstein, M.Siegel, C.Y.Kim, C.Khosla, and L.M.Sollid (2007).
Cyclic and dimeric gluten peptide analogues inhibiting DQ2-mediated antigen presentation in celiac disease.
  Bioorg Med Chem, 15, 6565-6573.  
17207708 R.J.Duquesnoy, and M.Askar (2007).
HLAMatchmaker: a molecularly based algorithm for histocompatibility determination. V. Eplet matching for HLA-DR, HLA-DQ, and HLA-DP.
  Hum Immunol, 68, 12-25.  
16464085 J.Xia, M.Siegel, E.Bergseng, L.M.Sollid, and C.Khosla (2006).
Inhibition of HLA-DQ2-mediated antigen presentation by analogues of a high affinity 33-residue peptide from alpha2-gliadin.
  J Am Chem Soc, 128, 1859-1867.  
15795926 J.Cluzeau, and W.D.Lubell (2005).
Design, synthesis, and application of azabicyclo[X.Y.0]alkanone amino acids as constrained dipeptide surrogates and peptide mimics.
  Biopolymers, 80, 98.  
14757758 G.J.Carven, S.Chitta, I.Hilgert, M.M.Rushe, R.F.Baggio, M.Palmer, J.E.Arenas, J.L.Strominger, V.Horejsi, L.Santambrogio, and L.J.Stern (2004).
Monoclonal antibodies specific for the empty conformation of HLA-DR1 reveal aspects of the conformational change associated with peptide binding.
  J Biol Chem, 279, 16561-16570.  
14748001 H.D.Schafroth, and C.A.Floudas (2004).
Predicting peptide binding to MHC pockets via molecular modeling, implicit solvation, and global optimization.
  Proteins, 54, 534-556.  
12952957 Z.Zavala-Ruiz, E.J.Sundberg, J.D.Stone, D.B.DeOliveira, I.C.Chan, J.Svendsen, R.A.Mariuzza, and L.J.Stern (2003).
Exploration of the P6/P7 region of the peptide-binding site of the human class II major histocompatability complex protein HLA-DR1.
  J Biol Chem, 278, 44904-44912.
PDB code: 1pyw
11857638 B.J.McFarland, and C.Beeson (2002).
Binding interactions between peptides and proteins of the class II major histocompatibility complex.
  Med Res Rev, 22, 168-203.  
11470892 B.J.McFarland, J.F.Katz, C.Beeson, and A.J.Sant (2001).
Energetic asymmetry among hydrogen bonds in MHC class II*peptide complexes.
  Proc Natl Acad Sci U S A, 98, 9231-9236.  
11745393 H.Beck, G.Schwarz, C.J.Schröter, M.Deeg, D.Baier, S.Stevanovic, E.Weber, C.Driessen, and H.Kalbacher (2001).
Cathepsin S and an asparagine-specific endoprotease dominate the proteolytic processing of human myelin basic protein in vitro.
  Eur J Immunol, 31, 3726-3736.  
16233088 H.Noguchi, T.Hanai, H.Honda, L.C.Harrison, and T.Kobayashi (2001).
Fuzzy neural network-based prediction of the motif for MHC class II binding peptides.
  J Biosci Bioeng, 92, 227-231.  
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