TY - JOUR
T1 - Prediction of MMP-9 Polymorphism Impacts on MDR-TB by Molecular Simulation and Network Interaction
AU - Messah, Anse Diana Valentiene
AU - Darmiati, Sawitri
AU - Rumende, Cleopas Marthin
AU - Soemarwoto, Retno Ariza
AU - Prihartono, Joedo
AU - Asmarinah, null
AU - Fadilah, Fadilah
AU - Prawiningrum, Aisyah Fitriannisa
N1 - Funding Information:
We are thankful to all authors who provided expertise that greatly assisted the research. This work was supported by Universitas Indonesia grant for International Indexed Publication (PUTI) Doctoral with Number: NKB-571/UN2.RST/HKP.05.00/2020.
Publisher Copyright:
© 2022 Phcogj.Com.
PY - 2022/11
Y1 - 2022/11
N2 - MMP-9 overexpression is associated with a poor outcome in MDR-TB patients, indicating that MMP-9 is a suitable target for MDR-TB therapy. MMP-9 also includes SNPs that occur at inhibitor binding areas as well as zinc ions. As a result of polymorphisms, the usage of MMP-9 inhibitors for MDR-TB might vary. Through molecular simulation, it has been found that the mutant MMP-9 has a larger cavity and a more lipophilic surface. The docking tests revealed that EGTA had the least amount of binding energy to both wild-type and mutant MMP-9. The wildtype MMP-9 can bind zinc when EGTA is in the active site. This shows that using EGTA to chelate Zn is only partially successful. However, the binding energy of EGTA at the active site suggests that it may be a competitor to MMP-9 substrates. On the other hand, Zn is not involved in the interaction of the mutant MMP-9-EGTA complex.
AB - MMP-9 overexpression is associated with a poor outcome in MDR-TB patients, indicating that MMP-9 is a suitable target for MDR-TB therapy. MMP-9 also includes SNPs that occur at inhibitor binding areas as well as zinc ions. As a result of polymorphisms, the usage of MMP-9 inhibitors for MDR-TB might vary. Through molecular simulation, it has been found that the mutant MMP-9 has a larger cavity and a more lipophilic surface. The docking tests revealed that EGTA had the least amount of binding energy to both wild-type and mutant MMP-9. The wildtype MMP-9 can bind zinc when EGTA is in the active site. This shows that using EGTA to chelate Zn is only partially successful. However, the binding energy of EGTA at the active site suggests that it may be a competitor to MMP-9 substrates. On the other hand, Zn is not involved in the interaction of the mutant MMP-9-EGTA complex.
KW - Gene polymorphism
KW - Matrix metalloproteinase 9
KW - Molecular simulation
KW - Multidrug resistant TB
UR - http://www.scopus.com/inward/record.url?scp=85159798959&partnerID=8YFLogxK
U2 - 10.5530/pj.2022.14.176
DO - 10.5530/pj.2022.14.176
M3 - Article
AN - SCOPUS:85159798959
SN - 0975-3575
VL - 14
SP - 833
EP - 841
JO - Pharmacognosy Journal
JF - Pharmacognosy Journal
IS - 6
ER -