NDLI: Mechanistic insights into mode of actions of novel oligopeptidase B inhibitors for combating leishmaniasis

Content Provider	Springer Nature Link
Author	Goyal, Sukriti Grover, Sonam Dhanjal, Jaspreet Kaur Goyal, Manisha Tyagi, Chetna Chacko, Sajeev Grover, Abhinav
Copyright Year	2014
Abstract	Leishmaniasis is an endemic disease caused by infection with one of several different species of protozoan parasite Leishmania. Oligopeptidase B (OPB) is a serine peptidase which plays a vital role in survival of the Leishmania parasite in the host (human) macrophage and help in attaining complete virulence. Inhibition of this peptidase would check the parasite growth inside the host organism and would thus control its infection. Lack of efficient and cheap drugs has led to an urgent need for development of new anti-leishmanial drugs and this study is a step forward in this direction. Using a structure-based approach we virtually screened a large naturally-occurring compound library against OPB and subjected two top scoring compounds with high binding affinity to molecular dynamics simulations which showed a stable RMSD trajectory. The first compound COP (Glide score: -13.183) was found stable for 15 ns at RMSD of 2.5 Å while the second compound TOA (Glide score: -10.308) was stable for 8 ns at RMSD of 1.5 Å. The screened compounds interacted with some crucial residues of OPB such as COP interacted with Ser577 and His697 (part of the catalytic triad), Tyr499 (responsible for substrate stability), Arg576 (conserved in protozoan family) and Arg664 (plays a role in stabilization of the bound inhibitor). TOA also interacted with Glu669 (conserved in protozoan family) in addition to the residues interacted with COA. These interactions are crucial for OPB inhibition. This study identified naturally-occurring compound leads against OPB with good binding affinity and low toxicity to human cells. Figure Mode of actions of novel Oligopeptidase B inhibitors before and after Molecular Dynamics Simulations.
Starting Page	1
Ending Page	9
Page Count	9
File Format	PDF
ISSN	16102940
Journal	Journal of Molecular Modeling
Volume Number	20
Issue Number	3
e-ISSN	09485023
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2014-02-25
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Leishmanial Leishmaniasis Inhibitor Oligopeptidase B Natural Virtual screening Computer Applications in Chemistry Molecular Medicine Computer Application in Life Sciences Characterization and Evaluation of Materials Theoretical and Computational Chemistry
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Physical and Theoretical Chemistry Computational Theory and Mathematics Catalysis Inorganic Chemistry Computer Science Applications

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Phenylethanoid glycosides as a possible COVID-19 protease inhibitor: a virtual screening approach.

Structural insights into mode of actions of novel natural Mycobacterium protein tyrosine phosphatase B inhibitors.

Probing the structure of Leishmania major DHFR TS and structure based virtual screening of peptide library for the identification of anti-leishmanial leads

In silico identification of novel kinase inhibitors by targeting B-Rafv660e from natural products database

Identification of and Mechanistic Insights into SARS-CoV-2 Main Protease Non-Covalent Inhibitors: An In-Silico Study.

Virtual screening for potential inhibitors of bacterial MurC and MurD ligases

Discovery of ERBB3 inhibitors for non-small cell lung cancer (NSCLC) via virtual screening

Crystal Structure of Inhibitor-Bound Bacterial Oligopeptidase B in the Closed State: Similarity and Difference between Protozoan and Bacterial Enzymes.

3D QSAR pharmacophore model based on diverse IKKβ inhibitors

Mechanistic insights into mode of actions of novel oligopeptidase B inhibitors for combating leishmaniasis

Similar Documents

Phenylethanoid glycosides as a possible COVID-19 protease inhibitor: a virtual screening approach.

Structural insights into mode of actions of novel natural Mycobacterium protein tyrosine phosphatase B inhibitors.

Probing the structure of Leishmania major DHFR TS and structure based virtual screening of peptide library for the identification of anti-leishmanial leads

In silico identification of novel kinase inhibitors by targeting B-Rafv660e from natural products database

Identification of and Mechanistic Insights into SARS-CoV-2 Main Protease Non-Covalent Inhibitors: An In-Silico Study.

Virtual screening for potential inhibitors of bacterial MurC and MurD ligases

Discovery of ERBB3 inhibitors for non-small cell lung cancer (NSCLC) via virtual screening

Crystal Structure of Inhibitor-Bound Bacterial Oligopeptidase B in the Closed State: Similarity and Difference between Protozoan and Bacterial Enzymes.

3D QSAR pharmacophore model based on diverse IKKβ inhibitors

Mechanistic insights into mode of actions of novel oligopeptidase B inhibitors for combating leishmaniasis