COMPARATIVE MODELING OF 3-OXOACYL-ACYL-CARRIER PROTEIN SYNTHASE I/II IN PLASMODIUM FALCIPARUM– A POTENT TARGET OF MALARIA

Mukesh Yadav¹, Anuraj Nayarisseri²*, Girish Singh Rajput³, Aditya Jain⁴, Ankit Verma⁵, Priyanka Gupta^6
1Eminent Biosciences, Bioinformatics Research Laboratory, Indore, M.P., India
²Eminent Biosciences, Bioinformatics Research Laboratory, Indore, M.P., India
³Department of Biotechnology, Devi Ahilya University, Indore, M.P., India
⁴Softvision College, Indore, M.P., India
⁵Softvision College, Indore, M.P., India
⁶Softvision College, Indore, M.P., India
* Corresponding Author : anuraj@eminentbio.com

Received : -     Accepted : -     Published : 15-06-2010
Volume : 2     Issue : 1       Pages : 1 - 4
Int J Bioinformatics Res 2.1 (2010):1-4
DOI : http://dx.doi.org/10.9735/0975-3087.2.1.1-4

Keywords : Comparative modeling, Fatty acid synthesis, ICM Molsoft, PROCHECK
Conflict of Interest : None declared

Plasmodium falciparum causing malaria is yet reigning against drug design community when it comes to survival and defense. Continuous evolution and drug resistant character is foremost basis of parasite’s versatility. 3-oxoacyl-acyl-carrier protein synthase I/II in Plasmodium falciparum is discovered decisive in fatty acid synthesis machinery. Objectives of enzyme inhibition need structural characterization from its 3D structure. In present studies molecular modeling of 3-oxoacyl-acyl-carrier protein synthase I/II is achieved using in silico comparative modeling. ICM Molsoft algorithm was adopted for comparative modeling which provides an accurate and efficient module to build loops and side chains found non-identical in sequence. Energy parameters fell in thermodynamically stability zone. Modeled structure revealed appreciable measures when validated. Ramachandran plot signified the present work undertaken through conformational parameters _ (phi) and _ (psi) angles calculated from model with 83.2% residues in most favoured region. Further PROCHECK results confirmed acceptance of model through main and side-chain values. Root mean square distance of planarity found below 0.01. Beside some bad contacts, bond angles and bond lengths confer qualitative part of work. Structure of 3-oxoacyl-acyl-carrier protein synthase I/II can be important tool for structure based drug designing techniques to impel the search of new efficient inhibitors. Comparison of similar structures of parasite can further reveal mutational trends to study their evolution patterns.

[1] World Malaria Report 2008. (2008) World Health Organisation. pp. 10. Retrieved 2009-08-17  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[2] Cavalier-Smith T. (1982) Biol. J. Linn. Soc. 17:289– 306  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[3] World Health Organization. The world health report (2000) World Health Organization, Geneva, Switzerland  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[4] Fish W. R. (1995) J. J. Marr and M. Muller (ed.), Biochemistry and molecular biology of parasites. Academic Press, London, United Kingdom, p. 133–145  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[5] Holz G. G. (1977) Bull. W. H. O. 55:237– 248.  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[6] Ralph S. et al. (2001) The apicoplast as an antimalarial drug target Drug Resistance Updates 4: 145–151  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[7] Waller R. F., Keeling P. J., Donald R. G. K., Striepen B., Handman E., Lang- Unnasch N., Cowman A. F., Besra G. S., Roos D. S. and McFadden G. I. (1998) Proc. Natl. Acad. Sci. USA 95:12352–12357  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[8] Waller R. F., Reed M. B., Cowman A. F., and McFadden G. I. (2000) EMBO J. 19:1794–1802  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[9] Bairoch A., Boeckmann B., Ferro S., Gasteiger E. (2004) Swiss-Prot. Brief. Bioinform. 5:39-55.  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[10] The UniProt Consortium The universal protein resource (UniProt) (2008) Nucleic Acids Res. 36:D190-195  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[11] Boeckmann B., Blatter M.-C., Famiglietti L., Hinz U., Lane L., Roechert B., Bairoch A. (2005) Comptes Rendus Biologies 328:882-99.  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[12] Schapira M., Raaka B.M., Samuels H.H. and Abagyan R. (2001) BMC Structural Biology 1:1.  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[13] Schapira M., Abagyan R. and Totrov M. (2002) BMC Struct Biol 2(1):1  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[14] Schapira M., Abagyan R. and Totrov M. (2003) J Med Chem 46(14):3045-3059  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[15] Abagyan R. and Totrov M. (1996) Abstr. Pap. Am. Chem. Soc. 211:35-COMP.  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[16] Totrov M. and Abagyan R. (2001) Biopolymers 60(2):124-133.  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[17] Borchert T.V., Abagyan R., Jaenicke R. and Wierenga R.K. (1994) Proc. Natl. Acad. Sci. U. S. A. 91(4):1515-1518  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[18] Borchert T.V., Kishan K.V., Zeelen J.P., Schliebs W., Thanki N., Abagyan R., Jaenicke R. and Wierenga R.K. (1995) Structure 3(7):669-679  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[19] Thanki N., Zeelen J.P., Mathieu M., Jaenicke R., Abagyan R.A., RWierenga K. and Schliebs W. (1997) Protein Eng 10(2):159-167  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[20] Laskowski R. A., MacArthur M. W., Moss D. S. and Thornton J. M. (1993) J. Appl. Cryst., 26, 283-291.  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[21] Morris A. L., MacArthur M. W., Hutchinson E. G. and Thornton J. M. (1992) Proteins, 12, 345-364  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[22] Allen F. H., Bellard S., Brice M. D., Cartwright B. A., Doubleday A., Higgs H., Hummelink T., Hummelink-Peters B.G., Kennard O., Motherwell W. D .S., Rodgers J. R. and Watson D. G. (1979) Acta Cryst., B35, 2331--2339  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[23] http://www.biochem.ucl.ac.uk  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus