PMID- 30067362
OWN - NLM
STAT- MEDLINE
DCOM- 20191009
LR  - 20191010
IS  - 1520-5207 (Electronic)
IS  - 1520-5207 (Linking)
VI  - 122
IP  - 33
DP  - 2018 Aug 23
TI  - Fragment Molecular Orbital Study of the Interaction between Sarco/Endoplasmic 
      Reticulum Ca(2+)-ATPase and its Inhibitor Thapsigargin toward Anti-Malarial 
      Development.
PG  - 7970-7977
LID - 10.1021/acs.jpcb.8b04509 [doi]
AB  - Plasmodium falciparum, the causative agent of malignant malaria, is insensitive 
      to thapsigargin (TG), a well-known inhibitor of the human sarco/endoplasmic 
      reticulum Ca(2+)-ATPase (SERCA). To understand the key factor causing the 
      difference of the sensitivity, the molecular interaction of TG and each SERCA was 
      analyzed by the fragment molecular orbital (FMO) method. While the major 
      component of the interaction energy was the nonpolar interaction, the major 
      difference in the molecular interaction arose from the polar interaction, namely, 
      the hydrogen bonding interaction with a hydroxyl group of TG. Additionally, we 
      successfully confirmed these FMO calculation results by measuring the inhibitory 
      activity of a synthesized TG derivative. Our calculations and experiments 
      indicated that, by replacing the hydroxyl group of TG with another functional 
      group, the sensitivities of TG to human and P. falciparum SERCAs can be reversed. 
      This study provides important information to develop antimalarial compounds 
      targeting P. falciparum SERCA.
FAU - Ishikawa, Takeshi
AU  - Ishikawa T
AUID- ORCID: 0000-0002-3187-1381
AD  - Department of Molecular Microbiology and Immunology, Graduate School of 
      Biomedical Sciences , Nagasaki University , 1-12-4 Sakamoto , Nagasaki 852-8523 , 
      Japan.
AD  - Leading Program, Graduate School of Biomedical Sciences , Nagasaki University , 
      1-12-4 Sakamoto , Nagasaki 852-8523 , Japan.
FAU - Mizuta, Satoshi
AU  - Mizuta S
AUID- ORCID: 0000-0002-9023-7671
AD  - Department of Molecular Microbiology and Immunology, Graduate School of 
      Biomedical Sciences , Nagasaki University , 1-12-4 Sakamoto , Nagasaki 852-8523 , 
      Japan.
FAU - Kaneko, Osamu
AU  - Kaneko O
AD  - Leading Program, Graduate School of Biomedical Sciences , Nagasaki University , 
      1-12-4 Sakamoto , Nagasaki 852-8523 , Japan.
AD  - Department of Protozoology, Institute of Tropical Medicine (NEKKEN) , Nagasaki 
      University , 1-12-4 Sakamoto , Nagasaki 852-8523 , Japan.
FAU - Yahata, Kazuhide
AU  - Yahata K
AD  - Department of Protozoology, Institute of Tropical Medicine (NEKKEN) , Nagasaki 
      University , 1-12-4 Sakamoto , Nagasaki 852-8523 , Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180814
PL  - United States
TA  - J Phys Chem B
JT  - The journal of physical chemistry. B
JID - 101157530
RN  - 0 (Antimalarials)
RN  - 0 (Protozoan Proteins)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Antimalarials/chemistry/*metabolism
MH  - Humans
MH  - Hydrogen Bonding
MH  - Models, Molecular
MH  - Plasmodium falciparum/enzymology
MH  - Protein Binding
MH  - Protozoan Proteins/chemistry/metabolism
MH  - Quantum Theory
MH  - Sarcoplasmic Reticulum Calcium-Transporting ATPases/chemistry/*metabolism
MH  - Sequence Alignment
MH  - Thapsigargin/analogs & derivatives/chemical synthesis/*metabolism
EDAT- 2018/08/02 06:00
MHDA- 2019/10/11 06:00
CRDT- 2018/08/02 06:00
PHST- 2018/08/02 06:00 [pubmed]
PHST- 2019/10/11 06:00 [medline]
PHST- 2018/08/02 06:00 [entrez]
AID - 10.1021/acs.jpcb.8b04509 [doi]
PST - ppublish
SO  - J Phys Chem B. 2018 Aug 23;122(33):7970-7977. doi: 10.1021/acs.jpcb.8b04509. Epub 
      2018 Aug 14.