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PDBsum entry 1rhh
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Immune system PDB id
1rhh

 

 

 

 

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Contents
Protein chains
215 a.a. *
233 a.a. *
Waters ×619
* Residue conservation analysis
PDB id:
1rhh
Name: Immune system
Title: Crystal structure of the broadly HIV-1 neutralizing fab x5 at 1.90 angstrom resolution
Structure: Fab x5, light chain. Chain: a, c. Engineered: yes. Fab x5, heavy chain. Chain: b, d. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
1.90Å     R-factor:   0.224     R-free:   0.227
Authors: R.Darbha,S.Phogat,A.F.Labrijn,Y.Shu,Y.Gu,M.Andrykovitch,M.Y.Zhang, R.Pantophlet,L.Martin,C.Vita,D.R.Burton,D.S.Dimitrov,X.Ji
Key ref:
R.Darbha et al. (2004). Crystal structure of the broadly cross-reactive HIV-1-neutralizing Fab X5 and fine mapping of its epitope. Biochemistry, 43, 1410-1417. PubMed id: 14769016 DOI: 10.1021/bi035323x
Date:
14-Nov-03     Release date:   24-Feb-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Q6GMV9  (Q6GMV9_HUMAN) - 
Protein chains
Q6PJF1  (Q6PJF1_HUMAN) - 
Key:    Secondary structure

 

 
DOI no: 10.1021/bi035323x Biochemistry 43:1410-1417 (2004)
PubMed id: 14769016  
 
 
Crystal structure of the broadly cross-reactive HIV-1-neutralizing Fab X5 and fine mapping of its epitope.
R.Darbha, S.Phogat, A.F.Labrijn, Y.Shu, Y.Gu, M.Andrykovitch, M.Y.Zhang, R.Pantophlet, L.Martin, C.Vita, D.R.Burton, D.S.Dimitrov, X.Ji.
 
  ABSTRACT  
 
The human monoclonal antibody Fab X5 neutralizes a broad range of HIV-1 primary isolates. The crystal structure of X5 has been determined at 1.9 A resolution. There are two crystallographically independent Fab fragments in the asymmetric unit. The crystallographic R value for the final model is 0.22. The antibody-combining site features a long (22 amino acid residues) CDR H3 with a protruding hook-shaped motif. The X5 structure and site-directed mutagenesis data suggest that X5 amino acid residues W100 and Y100F in the CDR H3 motif may be critical for the binding of Fab X5 to gp120. X5 bound to a complex of a CD4 mimetic and gp120 with approximately the same kinetics and affinity as to a CD4-gp120 complex, suggesting that specific interactions between CD4 and X5 are unlikely to contribute to the binding of X5 to gp120-CD4 complexes. Binding of X5 to alanine scanning mutants of gp120JR-CSF complexed with CD4 suggested a critical role of the highly conserved amino acid residues at positions 423 and 432. The X5 structure and fine mapping of its epitope may assist in the elucidation of the mechanisms of viral entry and neutralization, and the development of HIV-1 inhibitors and vaccines.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21252631 C.V.Hanson (2011).
Vaccinogenicity.
  AIDS, 25, 581-584.  
20335257 J.M.Binley, Y.E.Ban, E.T.Crooks, D.Eggink, K.Osawa, W.R.Schief, and R.W.Sanders (2010).
Role of complex carbohydrates in human immunodeficiency virus type 1 infection and resistance to antibody neutralization.
  J Virol, 84, 5637-5655.  
  20923574 M.Wen, R.Arora, H.Wang, L.Liu, J.T.Kimata, and P.Zhou (2010).
GPI-anchored single chain Fv--an effective way to capture transiently-exposed neutralization epitopes on HIV-1 envelope spike.
  Retrovirology, 7, 79.  
20822346 S.Paul, S.Planque, Y.Nishiyama, M.Escobar, and C.Hanson (2010).
Back to the future: covalent epitope-based HIV vaccine development.
  Expert Rev Vaccines, 9, 1027-1043.  
19785005 K.R.Clark, and S.T.Walsh (2009).
Crystal structure of a 3B3 variant-A broadly neutralizing HIV-1 scFv antibody.
  Protein Sci, 18, 2429-2441.
PDB code: 3juy
19729618 L.M.Walker, S.K.Phogat, P.Y.Chan-Hui, D.Wagner, P.Phung, J.L.Goss, T.Wrin, M.D.Simek, S.Fling, J.L.Mitcham, J.K.Lehrman, F.H.Priddy, O.A.Olsen, S.M.Frey, P.W.Hammond, S.Kaminsky, T.Zamb, M.Moyle, W.C.Koff, P.Poignard, D.R.Burton, G.Miiro, J.Serwanga, A.Pozniak, D.McPhee, O.Manigart, L.Mwananyanda, E.Karita, A.Inwoley, W.Jaoko, J.DeHovitz, L.G.Bekker, P.Pitisuttithum, R.Paris, and S.Allen (2009).
Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target.
  Science, 326, 285-289.  
19615335 X.Xiao, Y.Feng, B.K.Vu, R.Ishima, and D.S.Dimitrov (2009).
A large library based on a novel (CH2) scaffold: identification of HIV-1 inhibitors.
  Biochem Biophys Res Commun, 387, 387-392.  
18539308 E.T.Crooks, P.Jiang, M.Franti, S.Wong, M.B.Zwick, J.A.Hoxie, J.E.Robinson, P.L.Moore, and J.M.Binley (2008).
Relationship of HIV-1 and SIV envelope glycoprotein trimer occupation and neutralization.
  Virology, 377, 364-378.  
18838688 J.G.Joyce, I.J.Krauss, H.C.Song, D.W.Opalka, K.M.Grimm, D.D.Nahas, M.T.Esser, R.Hrin, M.Feng, V.Y.Dudkin, M.Chastain, J.W.Shiver, and S.J.Danishefsky (2008).
An oligosaccharide-based HIV-1 2G12 mimotope vaccine induces carbohydrate-specific antibodies that fail to neutralize HIV-1 virions.
  Proc Natl Acad Sci U S A, 105, 15684-15689.  
  18706111 S.Sourial, and C.Nilsson (2008).
HIV-2 neutralization by intact V3-specific Fab fragments.
  Virol J, 5, 96.  
17580087 E.T.Crooks, P.L.Moore, M.Franti, C.S.Cayanan, P.Zhu, P.Jiang, R.P.de Vries, C.Wiley, I.Zharkikh, N.Schülke, K.H.Roux, D.C.Montefiori, D.R.Burton, and J.M.Binley (2007).
A comparative immunogenicity study of HIV-1 virus-like particles bearing various forms of envelope proteins, particles bearing no envelope and soluble monomeric gp120.
  Virology, 366, 245-262.  
17516710 J.M.Gershoni, A.Roitburd-Berman, D.D.Siman-Tov, N.Tarnovitski Freund, and Y.Weiss (2007).
Epitope mapping: the first step in developing epitope-based vaccines.
  BioDrugs, 21, 145-156.  
17418361 R.Pantophlet, R.O.Aguilar-Sino, T.Wrin, L.A.Cavacini, and D.R.Burton (2007).
Analysis of the neutralization breadth of the anti-V3 antibody F425-B4e8 and re-assessment of its epitope fine specificity by scanning mutagenesis.
  Virology, 364, 441-453.  
17098740 S.Subramanian, E.T.Boder, and D.E.Discher (2007).
Phylogenetic divergence of CD47 interactions with human signal regulatory protein alpha reveals locus of species specificity. Implications for the binding site.
  J Biol Chem, 282, 1805-1818.  
16904645 V.Choudhry, M.Y.Zhang, I.Harris, I.A.Sidorov, B.Vu, A.S.Dimitrov, T.Fouts, and D.S.Dimitrov (2006).
Increased efficacy of HIV-1 neutralization by antibodies at low CCR5 surface concentration.
  Biochem Biophys Res Commun, 348, 1107-1115.  
16284180 C.C.Huang, M.Tang, M.Y.Zhang, S.Majeed, E.Montabana, R.L.Stanfield, D.S.Dimitrov, B.Korber, J.Sodroski, I.A.Wilson, R.Wyatt, and P.D.Kwong (2005).
Structure of a V3-containing HIV-1 gp120 core.
  Science, 310, 1025-1028.
PDB code: 2b4c
16151404 H.R.Hoogenboom (2005).
Selecting and screening recombinant antibody libraries.
  Nat Biotechnol, 23, 1105-1116.  
15867093 J.M.Decker, F.Bibollet-Ruche, X.Wei, S.Wang, D.N.Levy, W.Wang, E.Delaporte, M.Peeters, C.A.Derdeyn, S.Allen, E.Hunter, M.S.Saag, J.A.Hoxie, B.H.Hahn, P.D.Kwong, J.E.Robinson, and G.M.Shaw (2005).
Antigenic conservation and immunogenicity of the HIV coreceptor binding site.
  J Exp Med, 201, 1407-1419.  
16189008 R.A.Wilkinson, C.Piscitelli, M.Teintze, L.A.Cavacini, M.R.Posner, and C.M.Lawrence (2005).
Structure of the Fab fragment of F105, a broadly reactive anti-human immunodeficiency virus (HIV) antibody that recognizes the CD4 binding site of HIV type 1 gp120.
  J Virol, 79, 13060-13069.
PDB code: 1u6a
16252250 R.L.Rich, and D.G.Myszka (2005).
Survey of the year 2004 commercial optical biosensor literature.
  J Mol Recognit, 18, 431-478.  
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 code is shown on the right.

 

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