PMID- 9385550
OWN - NLM
STAT- MEDLINE
DCOM- 19971217
LR  - 20191102
IS  - 0920-654X (Print)
IS  - 0920-654X (Linking)
VI  - 11
IP  - 5
DP  - 1997 Sep
TI  - Fine specificity of antigen binding to two class I major histocompatibility 
      proteins (B*2705 and B*2703) differing in a single amino acid residue.
PG  - 463-78
AB  - Starting from the X-ray structure of a class I major histocompatibility complex 
      (MHC)-encoded protein (HLA-B*2705), a naturally presented self-nonapeptide and 
      two synthetic analogues were simulated in the binding groove of two human 
      leukocyte antigen (HLA) alleles (B*2703 and B*2705) differing in a single amino 
      acid residue. After 200 ps molecular dynamics simulations of the solvated 
      HLA-peptide pairs, some molecular properties of the complexes (distances between 
      ligand and protein center of masses, atomic fluctuations, buried versus 
      accessible surface areas, hydrogen-bond frequencies) allow a clear discrimination 
      of potent from weak MHC binders. The binding specificity of the three 
      nonapeptides for the two HLA alleles could be explained by the disruption of one 
      hydrogen-bonding network in the binding pocket of the HLA-B*2705 protein where 
      the single mutation occurs. Rearrangements of interactions in the B pocket, which 
      binds the side chain of peptide residue 2, and a weakening of interactions 
      involving the C-terminal end of the peptide also took place. In addition, 
      extension of the peptide backbone using a beta-Ala analogue did not abolish 
      binding to any of the two HLA-B27 subtypes, but increased the selectivity for 
      B*2703, as expected from the larger peptide binding groove in this subtype. A 
      better understanding of the atomic details involved in peptide selection by 
      closely related HLA alleles is of crucial importance for unraveling the molecular 
      features linking particular HLA alleles to autoimmune diseases, and for the 
      identification of antigenic peptides triggering such pathologies.
FAU - Rognan, D
AU  - Rognan D
AD  - Department of Pharmacy, Swiss Federal Institute of Technology, Zurich, 
      Switzerland.
FAU - Krebs, S
AU  - Krebs S
FAU - Kuonen, O
AU  - Kuonen O
FAU - Lamas, J R
AU  - Lamas JR
FAU - Lopez de Castro, J A
AU  - Lopez de Castro JA
FAU - Folkers, G
AU  - Folkers G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Comput Aided Mol Des
JT  - Journal of computer-aided molecular design
JID - 8710425
RN  - 0 (HLA-B27 Antigen)
RN  - 0 (Peptides)
SB  - IM
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - Crystallography, X-Ray
MH  - HLA-B27 Antigen/*chemistry
MH  - Humans
MH  - Hydrogen Bonding
MH  - Kinetics
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Peptides/chemistry/immunology
MH  - Protein Binding
MH  - Structure-Activity Relationship
MH  - Thermodynamics
EDAT- 1997/12/31 00:00
MHDA- 1997/12/31 00:01
CRDT- 1997/12/31 00:00
PHST- 1997/12/31 00:00 [pubmed]
PHST- 1997/12/31 00:01 [medline]
PHST- 1997/12/31 00:00 [entrez]
AID - 10.1023/a:1007963901092 [doi]
PST - ppublish
SO  - J Comput Aided Mol Des. 1997 Sep;11(5):463-78. doi: 10.1023/a:1007963901092.