The Possible Mechanism of Idiosyncratic Lapatinib-Induced Liver Injury in Patients Carrying Human Leukocyte Antigen-DRB1*07:01.
Idiosyncratic lapatinib-induced liver injury has been reported to be associated with human leukocyte antigen (HLA)-DRB1*07:01. In order to investigate its mechanism, interaction of lapatinib with HLA-DRB1*07:01 and its ligand peptide derived from tetanus toxoid, has been evaluated in vitro. Here we...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4476721?pdf=render |
| _version_ | 1828335100287254528 |
|---|---|
| author | Makoto Hirasawa Katsunobu Hagihara Noriko Okudaira Takashi Izumi |
| author_facet | Makoto Hirasawa Katsunobu Hagihara Noriko Okudaira Takashi Izumi |
| author_sort | Makoto Hirasawa |
| collection | DOAJ |
| description | Idiosyncratic lapatinib-induced liver injury has been reported to be associated with human leukocyte antigen (HLA)-DRB1*07:01. In order to investigate its mechanism, interaction of lapatinib with HLA-DRB1*07:01 and its ligand peptide derived from tetanus toxoid, has been evaluated in vitro. Here we show that lapatinib enhances binding of the ligand peptide to HLA-DRB1*07:01. Furthermore in silico molecular dynamics analysis revealed that lapatinib could change the β chain helix in the HLA-DRB1*07:01 specifically to form a tightly closed binding groove structure and modify a large part of the binding groove. These results indicate that lapatinib affects the ligand binding to HLA-DRB1*07:01 and idiosyncratic lapatinib-induced liver injury might be triggered by this mechanism. This is the first report showing that the clinically available drug can enhance the binding of ligand peptide to HLA class II molecules in vitro and in silico. |
| first_indexed | 2024-04-13T21:41:23Z |
| format | Article |
| id | doaj.art-26206f8af9d74fddb4ba9beb22e7c36f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T21:41:23Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-26206f8af9d74fddb4ba9beb22e7c36f2022-12-22T02:28:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01106e013092810.1371/journal.pone.0130928The Possible Mechanism of Idiosyncratic Lapatinib-Induced Liver Injury in Patients Carrying Human Leukocyte Antigen-DRB1*07:01.Makoto HirasawaKatsunobu HagiharaNoriko OkudairaTakashi IzumiIdiosyncratic lapatinib-induced liver injury has been reported to be associated with human leukocyte antigen (HLA)-DRB1*07:01. In order to investigate its mechanism, interaction of lapatinib with HLA-DRB1*07:01 and its ligand peptide derived from tetanus toxoid, has been evaluated in vitro. Here we show that lapatinib enhances binding of the ligand peptide to HLA-DRB1*07:01. Furthermore in silico molecular dynamics analysis revealed that lapatinib could change the β chain helix in the HLA-DRB1*07:01 specifically to form a tightly closed binding groove structure and modify a large part of the binding groove. These results indicate that lapatinib affects the ligand binding to HLA-DRB1*07:01 and idiosyncratic lapatinib-induced liver injury might be triggered by this mechanism. This is the first report showing that the clinically available drug can enhance the binding of ligand peptide to HLA class II molecules in vitro and in silico.http://europepmc.org/articles/PMC4476721?pdf=render |
| spellingShingle | Makoto Hirasawa Katsunobu Hagihara Noriko Okudaira Takashi Izumi The Possible Mechanism of Idiosyncratic Lapatinib-Induced Liver Injury in Patients Carrying Human Leukocyte Antigen-DRB1*07:01. PLoS ONE |
| title | The Possible Mechanism of Idiosyncratic Lapatinib-Induced Liver Injury in Patients Carrying Human Leukocyte Antigen-DRB1*07:01. |
| title_full | The Possible Mechanism of Idiosyncratic Lapatinib-Induced Liver Injury in Patients Carrying Human Leukocyte Antigen-DRB1*07:01. |
| title_fullStr | The Possible Mechanism of Idiosyncratic Lapatinib-Induced Liver Injury in Patients Carrying Human Leukocyte Antigen-DRB1*07:01. |
| title_full_unstemmed | The Possible Mechanism of Idiosyncratic Lapatinib-Induced Liver Injury in Patients Carrying Human Leukocyte Antigen-DRB1*07:01. |
| title_short | The Possible Mechanism of Idiosyncratic Lapatinib-Induced Liver Injury in Patients Carrying Human Leukocyte Antigen-DRB1*07:01. |
| title_sort | possible mechanism of idiosyncratic lapatinib induced liver injury in patients carrying human leukocyte antigen drb1 07 01 |
| url | http://europepmc.org/articles/PMC4476721?pdf=render |
| work_keys_str_mv | AT makotohirasawa thepossiblemechanismofidiosyncraticlapatinibinducedliverinjuryinpatientscarryinghumanleukocyteantigendrb10701 AT katsunobuhagihara thepossiblemechanismofidiosyncraticlapatinibinducedliverinjuryinpatientscarryinghumanleukocyteantigendrb10701 AT norikookudaira thepossiblemechanismofidiosyncraticlapatinibinducedliverinjuryinpatientscarryinghumanleukocyteantigendrb10701 AT takashiizumi thepossiblemechanismofidiosyncraticlapatinibinducedliverinjuryinpatientscarryinghumanleukocyteantigendrb10701 AT makotohirasawa possiblemechanismofidiosyncraticlapatinibinducedliverinjuryinpatientscarryinghumanleukocyteantigendrb10701 AT katsunobuhagihara possiblemechanismofidiosyncraticlapatinibinducedliverinjuryinpatientscarryinghumanleukocyteantigendrb10701 AT norikookudaira possiblemechanismofidiosyncraticlapatinibinducedliverinjuryinpatientscarryinghumanleukocyteantigendrb10701 AT takashiizumi possiblemechanismofidiosyncraticlapatinibinducedliverinjuryinpatientscarryinghumanleukocyteantigendrb10701 |