NDLI: Molecular Modeling and Docking Studies of O-Succinylbenzoate Synthase of M. tuberculosis—a Potential Target for Antituberculosis Drug Design

Content Provider	Springer Nature Link
Author	Pulaganti, Madhusudana Banaganapalli, Babajan Mulakayala, Chaitanya Chitta, Suresh Kumar C. M., Anuradha
Copyright Year	2013
Abstract	Menaquinone is a lipid-soluble naphthoquinone that is essential for various pivotal functions of bacteria. Naphthoquinone is synthesized from chorismate of the shikimate pathway in microorganisms. Due to its absence in humans and animals, menaquinone biosynthesis has been an attractive target for development of antibiotics against a number of important microbial pathogens, such as Mycobacterium tuberculosis (Mtb). In shikimate pathway, O-succinylbenzoate synthase (OSBS) plays a major role and is one of the major potential drug targets. For Mtb-OSBS, a systematic study was conducted to get an insight about Mtb-OSBS enzyme and the corresponding inhibitors using in silico methods. The 3-D model of Mtb-OSBS was built using structure coordinates of Thermobifida fusca. O-succinylbenzoate synthase, the model, was further refined. The active site amino acids have been identified by comparing the template sequence with the Mtb-OSBS sequence. We identified that Lys$^{108}$, Asn$^{140}$, Asp$^{138}$, Lys$^{110}$, Glu$^{189}$, Ser$^{236}$, Asp$^{188}$, Arg$^{27}$, Tyr$^{52}$, and Ser$^{237}$ are highly conserved, and these may play a vital role as active residues, similar to that in template protein. As per the competitive binding of substrate (2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC)), we screened the SHCHC through AutoDock 4.0. The SHCHC molecule was further modified structurally and optimized through PRODRG server. Docking of the 12 lead molecules for best interactions with Mtb-OSBS has given an insight that all the lead molecules have shown interactions with active site amino acids of Mtb-OSBS. MD simulation analysis report has shown the stable conformation annotations of Mtb-OSBS. These hypothetical studies create another way to develop more potential drugs against the deadly mycobacterium.
Starting Page	1407
Ending Page	1432
Page Count	26
File Format	PDF
ISSN	02732289
Journal	Applied Biochemistry and Biotechnology
Volume Number	172
Issue Number	3
e-ISSN	15590291
Language	English
Publisher	Springer US
Publisher Date	2013-11-09
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Shikimate pathway Mtb-OSBS AutoDock 4.0 MD simulation Biotechnology Biochemistry
Content Type	Text
Resource Type	Article
Subject	Medicine Molecular Biology Environmental Engineering Biochemistry Bioengineering Applied Microbiology and Biotechnology Biotechnology

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