NDLI: Identification of Residues Involved in Substrate Specificity and Cytotoxicity of Two Closely Related Cutinases from Mycobacterium tuberculosis

Content Provider	PubMed Central
Author	Dedieu, Luc Carole, Serveau-avesque Canaan, Stéphane
Editor	Tyagi, Anil Kumar
Copyright Year	2013
Abstract	The enzymes belonging to the cutinase family are serine enzymes active on a large panel of substrates such as cutin, triacylglycerols, and phospholipids. In the M. tuberculosis H37Rv genome, seven genes coding for cutinase-like proteins have been identified with strong immunogenic properties suggesting a potential role as vaccine candidates. Two of these enzymes which are secreted and highly homologous, possess distinct substrates specificities. Cfp21 is a lipase and Cut4 is a phospholipase A2, which has cytotoxic effects on macrophages. Structural overlay of their three-dimensional models allowed us to identify three areas involved in the substrate binding process and to shed light on this substrate specificity. By site-directed mutagenesis, residues present in these Cfp21 areas were replaced by residues occurring in Cut4 at the same location. Three mutants acquired phospholipase A1 and A2 activities and the lipase activities of two mutants were 3 and 15 fold greater than the Cfp21 wild type enzyme. In addition, contrary to mutants with enhanced lipase activity, mutants that acquired phospholipase B activities induced macrophage lysis as efficiently as Cut4 which emphasizes the relationship between apparent phospholipase A2 activity and cytotoxicity. Modification of areas involved in substrate specificity, generate recombinant enzymes with higher activity, which may be more immunogenic than the wild type enzymes and could therefore constitute promising candidates for antituberculous vaccine production.
Related Links	http://dx.doi.org/10.1371/journal.pone.0066913
Starting Page	66913
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	7
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2013-07-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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

Rv2607 from Mycobacterium tuberculosis Is a Pyridoxine 5′-Phosphate Oxidase with Unusual Substrate Specificity

Enzymatic Activities and DNA Substrate Specificity of Mycobacterium tuberculosis DNA Helicase XPB

Dissecting the Role of Critical Residues and Substrate Preference of a Fatty Acyl-CoA Synthetase (FadD13) of Mycobacterium tuberculosis

Identification and Characterization of Lipase Activity and Immunogenicity of LipL from Mycobacterium tuberculosis

Identification of Genes to Differentiate Closely Related Salmonella Lineages

Identification of DNA Binding Motifs of the Mycobacterium tuberculosis PhoP/PhoR Two-Component Signal Transduction System

The Two PPX-GppA Homologues from Mycobacterium tuberculosis Have Distinct Biochemical Activities

Redesign of substrate specificity and identification of aminoglycoside binding residues of Eis from Mycobacterium tuberculosis

Ferritin Structure from Mycobacterium tuberculosis: Comparative Study with Homologues Identifies Extended C-Terminus Involved in Ferroxidase Activity

Identification of Residues Involved in Substrate Specificity and Cytotoxicity of Two Closely Related Cutinases from Mycobacterium tuberculosis

Similar Documents

Rv2607 from Mycobacterium tuberculosis Is a Pyridoxine 5′-Phosphate Oxidase with Unusual Substrate Specificity

Enzymatic Activities and DNA Substrate Specificity of Mycobacterium tuberculosis DNA Helicase XPB

Dissecting the Role of Critical Residues and Substrate Preference of a Fatty Acyl-CoA Synthetase (FadD13) of Mycobacterium tuberculosis

Identification and Characterization of Lipase Activity and Immunogenicity of LipL from Mycobacterium tuberculosis

Identification of Genes to Differentiate Closely Related Salmonella Lineages

Identification of DNA Binding Motifs of the Mycobacterium tuberculosis PhoP/PhoR Two-Component Signal Transduction System

The Two PPX-GppA Homologues from Mycobacterium tuberculosis Have Distinct Biochemical Activities

Redesign of substrate specificity and identification of aminoglycoside binding residues of Eis from Mycobacterium tuberculosis

Ferritin Structure from Mycobacterium tuberculosis: Comparative Study with Homologues Identifies Extended C-Terminus Involved in Ferroxidase Activity

Identification of Residues Involved in Substrate Specificity and Cytotoxicity of Two Closely Related Cutinases from Mycobacterium tuberculosis