PMID- 28870516
OWN - NLM
STAT- MEDLINE
DCOM- 20180720
LR  - 20180720
IS  - 1873-569X (Electronic)
IS  - 0923-1811 (Linking)
VI  - 88
IP  - 3
DP  - 2017 Dec
TI  - A docking model of dapsone bound to HLA-B*13:01 explains the risk of dapsone 
      hypersensitivity syndrome.
PG  - 320-329
LID - S0923-1811(17)30539-X [pii]
LID - 10.1016/j.jdermsci.2017.08.007 [doi]
AB  - BACKGROUND: Dapsone (4,4'-diaminodiphenylsulfone) has been widely used for the 
      treatment of infections such as leprosy. Dapsone hypersensitivity syndrome (DHS) 
      is a major side effect, developing in 0.5-3.6% of patients treated with dapsone, 
      and its mortality rate is  approximately 10%. Recently, human leukocyte antigen (HLA)-B*13:01 
      was identified as a marker of susceptibility to DHS. OBJECTIVES: To investigate 
      why HLA-B*13:01 is responsible for DHS from a structural point of view. METHODS: 
      First, we used homology modeling to derive the three-dimensional structures of 
      HLA-B*13:01 (associated with DHS) and HLA-B*13:02 (not so associated despite 
      strong sequence identity [99%] with HLA-B*13:01). Next, we used molecular 
      docking, molecular dynamic simulations, and the molecular mechanics 
      Poisson-Boltzman surface area method, to investigate the interactions of dapsone 
      with HLA-B*13:01 and 13:02. RESULTS: We found a crucial structural difference 
      between HLA-B*13:01 and 13:02 in the F-pocket of the antigen-binding site. As 
      Trp95 in the alpha-domain of HLA-B*13:02 is replaced with the less bulky Ile95 in 
      HLA-B*13:01, we found an additional well-defined sub-pocket within the 
      antigen-binding site of HLA-B*13:01. All three representative docking poses of 
      dapsone against the antigen-binding site of HLA-B*13:01 used this unique 
      sub-pocket, indicating its suitability for binding dapsone. However, HLA-B*13:02 
      does not seem to possess a binding pocket suitable for binding dapsone. Finally, 
      a binding free energy calculation combined with a molecular dynamics simulation 
      and the molecular mechanics Poisson-Boltzman surface area method indicated that 
      the binding affinity of dapsone for HLA-B*13:01 would be much greater than that 
      for HLA-B*13:02. CONCLUSIONS: Our computational results suggest that dapsone 
      would fit within the structure of the antigen-recognition site of HLA-B*13:01. 
      This may change the self-peptides that bind to HLA-B*13:01, explaining why 
      HLA-B*13:01 is a marker of DHS susceptibility.
CI  - Copyright (c) 2017 Japanese Society for Investigative Dermatology. Published by 
      Elsevier B.V. All rights reserved.
FAU - Watanabe, Hideaki
AU  - Watanabe H
AD  - Department of Dermatology, Showa University School of Medicine, Tokyo, Japan. 
      Electronic address: hwatanabe@med.showa-u.ac.jp.
FAU - Watanabe, Yurie
AU  - Watanabe Y
AD  - Department of Analytical and Physical Chemistry, Showa University School of 
      Pharmacy, Tokyo, Japan.
FAU - Tashiro, Yasuya
AU  - Tashiro Y
AD  - Department of Dermatology, Showa University School of Medicine, Tokyo, Japan.
FAU - Mushiroda, Taisei
AU  - Mushiroda T
AD  - RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
FAU - Ozeki, Takeshi
AU  - Ozeki T
AD  - RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
FAU - Hashizume, Hideo
AU  - Hashizume H
AD  - Department of Dermatology, Shimada Municipal Hospital, Shizuoka, Japan.
FAU - Sueki, Hirohiko
AU  - Sueki H
AD  - Department of Dermatology, Showa University School of Medicine, Tokyo, Japan.
FAU - Yamamoto, Toshinori
AU  - Yamamoto T
AD  - Showa University Medical Foundation, Showa University School of Pharmacy, Tokyo, 
      Japan.
FAU - Utsunomiya-Tate, Naoko
AU  - Utsunomiya-Tate N
AD  - Laboratory of Chemistry, Faculty of Pharma Sciences, Teikyo University, Tokyo, 
      Japan.
FAU - Gouda, Hiroaki
AU  - Gouda H
AD  - Department of Analytical and Physical Chemistry, Showa University School of 
      Pharmacy, Tokyo, Japan. Electronic address: godah@pharm.showa-u.ac.jp.
FAU - Kusakabe, Yoshio
AU  - Kusakabe Y
AD  - Department of Analytical and Physical Chemistry, Showa University School of 
      Pharmacy, Tokyo, Japan; Laboratory of Chemistry, Faculty of Pharma Sciences, 
      Teikyo University, Tokyo, Japan.
LA  - eng
PT  - Journal Article
DEP - 20170824
PL  - Netherlands
TA  - J Dermatol Sci
JT  - Journal of dermatological science
JID - 9011485
RN  - 0 (HLA-B Antigens)
RN  - 0 (Leprostatic Agents)
RN  - 8W5C518302 (Dapsone)
SB  - IM
MH  - Computational Biology
MH  - Dapsone/adverse effects/immunology/*metabolism
MH  - Drug Hypersensitivity Syndrome/etiology/*immunology
MH  - HLA-B Antigens/immunology/*metabolism
MH  - Humans
MH  - Leprostatic Agents/adverse effects/*metabolism
MH  - Leprosy/*drug therapy
MH  - Molecular Docking Simulation
MH  - Molecular Dynamics Simulation
MH  - Protein Binding
MH  - Sequence Homology, Amino Acid
OTO - NOTNLM
OT  - Binding affinity
OT  - Dapsone hypersensitivity syndrome
OT  - Docking simulation
OT  - HLA-B*13:01
OT  - Molecular structure
EDAT- 2017/09/06 06:00
MHDA- 2018/07/22 06:00
CRDT- 2017/09/06 06:00
PHST- 2017/04/04 00:00 [received]
PHST- 2017/07/04 00:00 [revised]
PHST- 2017/08/08 00:00 [accepted]
PHST- 2017/09/06 06:00 [pubmed]
PHST- 2018/07/22 06:00 [medline]
PHST- 2017/09/06 06:00 [entrez]
AID - S0923-1811(17)30539-X [pii]
AID - 10.1016/j.jdermsci.2017.08.007 [doi]
PST - ppublish
SO  - J Dermatol Sci. 2017 Dec;88(3):320-329. doi: 10.1016/j.jdermsci.2017.08.007. Epub 
      2017 Aug 24.