A systematic classification of Plasmodium falciparum P-loop NTPases: structural and functional correlation.
BACKGROUND
The P-loop NTPases constitute one of the largest groups of globular protein domains that play highly diverse functional roles in most of the organisms. Even with the availability of nearly 300 different Hidden Markov Models representing the P-loop NTPase superfamily, not many P-loop NTPases are known in Plasmodium falciparum. A number of characteristic attributes of the genome have resulted into the lack of knowledge about this functionally diverse, but important class of proteins.


METHODS
In the study, protein sequences with characteristic motifs of NTPase domain (Walker A and Walker B) are computationally extracted from the P. falciparum database. A detailed secondary structure analysis, functional classification, phylogenetic and orthology studies of the NTPase domain of repertoire of 97 P. falciparum P-loop NTPases is carried out.


RESULTS
Based upon distinct sequence features and secondary structure profile of the P-loop domain of obtained sequences, a cladistic classification is also conceded: nucleotide kinases and GTPases, ABC and SMC family, SF1/2 helicases, AAA+ and AAA protein families. Attempts are made to identify any ortholog(s) for each of these proteins in other Plasmodium sp. as well as its vertebrate host, Homo sapiens. A number of P. falciparum P-loop NTPases that have no homologue in the host, as well as those annotated as hypothetical proteins and lack any characteristic functional domain are identified.


CONCLUSIONS
The study suggests a strong correlation between sequence and secondary structure profile of P-loop domains and functional roles of these proteins and thus provides an opportunity to speculate the role of many hypothetical proteins. The study provides a methodical framework for the characterization of biologically diverse NTPases in the P. falciparum genome.The efforts made in the analysis are first of its kind; and the results augment to explore the functional role of many of these proteins from the parasite that could provide leads to identify novel drug targets against malaria.
Malaria Group, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India. deepti@icgeb.res.in
Deepti
D
Gangwar
Mridul K
MK
Kalita
Dinesh
D
Gupta
Virander S
VS
Chauhan
Asif
A
Mohmmed
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology; D017124:Conserved Sequence; D019143:Evolution, Molecular; D020558:GTP Phosphohydrolases / Q000145:classification / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D043583:Nucleoside-Triphosphatase / Q000737:chemistry / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000235:genetics* / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D020558:GTP Phosphohydrolases; D043583:Nucleoside-Triphosphatase