Structural and Functional analysis of Staphylococcus aureus NADP-dependent IDH and its comparison with Bacterial and Human NADP-dependent IDH



Uppu Venkateswara Prasad1, Vimjam Swarupa1, Sthanikam Yeswanth1, Pasupuleti Santhosh Kumar1, Easambadi Siva Kumar1, Kalikiri Mahesh Kumar Reddy1, Yellapu Nanda Kumar2, Vangavaragu Jhansi Rani4, Abhijit Chaudhary3, Potukuchi Venkata Gurunadha Krishna Sarma1*



1Department of Biotechnology, Sri Venkateswara Institute of Medical Sciences, Tirupati, AP, India, 517507; 2Department of Zoology, Sri Venkateswara University, Tirupati, AP, India, 517502; 3Department of Microbiology, Sri Venkateswara Institute of Medical Sciences, Tirupati - 517 507; 4Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS 66047, USA


Email; *Corresponding author


Article Type




Received January 23, 2014; Accepted January 31, 2014; Published February 19, 2014



Staphylococcus aureus a natural inhabitant of nasopharyngeal tract mainly survives as biofilms and possess complete Krebs cycle which plays major role in its pathogenesis. This TCA cycle is regulated by Isocitrate dehydrogenase (IDH) we have earlier cloned, sequenced (HM067707), expressed and characterized this enzyme from S. aureus ATCC12600. We have observed only one type of IDH in all the strains of S. aureus which dictates the flow of carbon thereby controlling the virulence and biofilm formation, this phenomenon is variable among bacteria. Therefore in the present study comparative structural and functional analysis of IDH was undertaken. As the crystal structure of S. aureus IDH was not available therefore using the deduced amino sequence of complete gene the 3D structure of IDH was built in Modeller 9v8. The PROCHECK and ProSAweb analysis showed the built structure was close to the crystal structure of Bacillus subtilis. This structure when superimposed with other bacterial IDH structures exhibited extensive structural variations as evidenced from the RMSD values correlating with extensive sequential variations. Only 24% sequence identity was observed with both human NADP dependent IDHs (PDB: 1T09 and 1T0L) and the structural comparative studies indicated extensive structural variations with an RMSD values of 14.284 and 10.073 respectively. Docking of isocitrate to both human IDHs and S. aureus IDH structures showed docking scores of -11.6169 and -10.973 respectively clearly indicating higher binding affinity of isocitrate to human IDH.



Isocitrate dehydrogenase, NADP, RMSD, TCA Cycle



Prasad  et al. Bioinformation 10(2): 081-086 (2014)

Edited by

P Kangueane






Biomedical Informatics



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