PMID- 26488421
OWN - NLM
STAT- MEDLINE
DCOM- 20170224
LR  - 20170817
IS  - 1538-0254 (Electronic)
IS  - 0739-1102 (Linking)
VI  - 34
IP  - 8
DP  - 2016 Aug
TI  - Structural modeling of HLA-B*1502/peptide/carbamazepine/T-cell receptor complex 
      architecture: implication for the molecular mechanism of carbamazepine-induced 
      Stevens-Johnson syndrome/toxic epidermal necrolysis.
PG  - 1806-17
LID - 10.1080/07391102.2015.1092476 [doi]
AB  - Drug-induced adverse reactions are a significant problem in healthcare worldwide 
      and are estimated to cost billions of dollars annually in the United States. A 
      portion of such reactions is observed to strongly associate with certain human 
      leukocyte antigen (HLA) alleles; one of the strongest associations is the 
      HLA-B*1502 protein with carbamazepine (CBZ)-induced Stevens-Johnson 
      syndrome/toxic epidermal necrolysis (SJS/TEN) - the odds ratio value can even be 
      higher than one thousand. The particularly strong association in CBZ-induced 
      SJS/TEN suggests that the HLA-B*1502 is not only a genetic marker but also a 
      participant in the pathogenesis of the disease. In the current study, we attempt 
      to computationally model the atomic-level structure of the complete 
      HLA-B*1502/peptide/CBZ/T-cell receptor (TCR) complex architecture based on prior 
      knowledge obtained from epidemiological investigations as well as in vitro and in 
      vivo assays. The model tells a different story about the molecular mechanism of 
      CBZ-induced SJS/TEN from that previously reported for abacavir (ABC)-induced 
      hypersensitivity (HSR); the CBZ molecule is located at the interface between 
      HLA-B*1502/peptide and TCR, directly contacts the P3-P6 residues of antigen 
      peptide, and bound within a pocket region encompassed by two TCR CDR3 fingers. 
      Molecular dynamics simulation and binding energy analysis further reveal that the 
      CBZ shows considerably high affinity to TCR over HLA-B*1502/peptide, which can 
      tightly interact with the former rather than the latter. From the model, two 
      hypotheses are proposed that can well explain most previous observations and are 
      expected to guide next wet-lab experiments. This study could help to promote our 
      understanding of the molecular mechanism and pathological implication underlying 
      CBZ-induced SJS/TEN.
FAU - Zhou, Peng
AU  - Zhou P
AD  - a Center of Bioinformatics (COBI), Key Laboratory for Neuroinformation of the 
      Ministry of Education, Center for Information in BioMedicine, School of Life 
      Science and Technology , University of Electronic Science and Technology of China 
      (UESTC) , Chengdu 610054 , China.
FAU - Zhang, Shilei
AU  - Zhang S
AD  - a Center of Bioinformatics (COBI), Key Laboratory for Neuroinformation of the 
      Ministry of Education, Center for Information in BioMedicine, School of Life 
      Science and Technology , University of Electronic Science and Technology of China 
      (UESTC) , Chengdu 610054 , China.
FAU - Wang, Yewang
AU  - Wang Y
AD  - a Center of Bioinformatics (COBI), Key Laboratory for Neuroinformation of the 
      Ministry of Education, Center for Information in BioMedicine, School of Life 
      Science and Technology , University of Electronic Science and Technology of China 
      (UESTC) , Chengdu 610054 , China.
FAU - Yang, Chao
AU  - Yang C
AD  - a Center of Bioinformatics (COBI), Key Laboratory for Neuroinformation of the 
      Ministry of Education, Center for Information in BioMedicine, School of Life 
      Science and Technology , University of Electronic Science and Technology of China 
      (UESTC) , Chengdu 610054 , China.
FAU - Huang, Jian
AU  - Huang J
AD  - a Center of Bioinformatics (COBI), Key Laboratory for Neuroinformation of the 
      Ministry of Education, Center for Information in BioMedicine, School of Life 
      Science and Technology , University of Electronic Science and Technology of China 
      (UESTC) , Chengdu 610054 , China.
LA  - eng
PT  - Journal Article
DEP - 20151214
PL  - England
TA  - J Biomol Struct Dyn
JT  - Journal of biomolecular structure & dynamics
JID - 8404176
RN  - 0 (HLA-B Antigens)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 33CM23913M (Carbamazepine)
SB  - IM
MH  - Binding Sites
MH  - Carbamazepine/adverse effects/*chemistry
MH  - HLA-B Antigens/*chemistry/genetics/metabolism
MH  - Humans
MH  - Models, Biological
MH  - *Models, Molecular
MH  - *Molecular Conformation
MH  - Mutation
MH  - Peptides/*chemistry/genetics/metabolism
MH  - Protein Binding
MH  - Receptors, Antigen, T-Cell/*chemistry/genetics/metabolism
MH  - Stevens-Johnson Syndrome/etiology
MH  - Structure-Activity Relationship
OTO - NOTNLM
OT  - CBZ-induced SJS/TEN
OT  - HLA-B*1502
OT  - HLA-drug association
OT  - T-cell receptor
OT  - adverse drug reaction
OT  - peptide
EDAT- 2015/10/22 06:00
MHDA- 2017/02/25 06:00
CRDT- 2015/10/22 06:00
PHST- 2015/10/22 06:00 [entrez]
PHST- 2015/10/22 06:00 [pubmed]
PHST- 2017/02/25 06:00 [medline]
AID - 10.1080/07391102.2015.1092476 [doi]
PST - ppublish
SO  - J Biomol Struct Dyn. 2016 Aug;34(8):1806-17. doi: 10.1080/07391102.2015.1092476. 
      Epub 2015 Dec 14.