Dendrimeric template of Plasmodium falciparum histidine rich protein II repeat motifs bearing Asp→Asn mutation exhibits heme binding and β-hematin formation.
Plasmodium falciparum (Pf) employs a crucial PfHRPII catalyzed reaction that converts toxic heme into hemozoin. Understanding heme polymerization mechanism is the first step for rational design of new drugs, targeting this pathway. Heme binding and hemozoin formation have been ascribed to PfHRPII aspartate carboxylate-heme metal ionic interactions. To investigate, if this ionic interaction is indeed pivotal, we examined the comparative heme binding and β-hematin forming abilities of a wild type dendrimeric peptide BNT1 {harboring the native sequence motif of PfHRPII (AHHAHHAADA)} versus a mutant dendrimeric peptide BNTM {in which ionic Aspartate residues have been replaced by the neutral Asparaginyl residues (AHHAHHAANA)}. UV and IR data reported here reveal that at pH 5, both BNT1 and BNTM exhibit comparable heme binding as well as β-hematin forming abilities, thus questioning the role of PfHRPII aspartate carboxylate-heme metal ionic interactions in heme binding and β-hematin formation. Based on our data and information in the literature we suggest the possible role of weak dispersive interactions like N-H···π and lone-pair···π in heme binding and hemozoin formation.
Malaria Research Laboratory, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
Pinky
P
Kumari
Malaria Research Laboratory, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
Dinkar
D
Sahal
Malaria Research Laboratory, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
Virander S
VS
Chauhan
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000953:Antigens, Protozoan / Q000737:chemistry*; D001216:Asparagine / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics; D001639:Bicarbonates / Q000378:metabolism; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D050091:Dendrimers / Q000737:chemistry*; D006418:Heme / Q000378:metabolism*; D006420:Hemeproteins / Q000378:metabolism*; D007700:Kinetics; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010963:Plasmodium falciparum; D011485:Protein Binding; D055550:Protein Stability; D015800:Protozoan Proteins / Q000737:chemistry*; D020449:Repetitive Sequences, Amino Acid; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship; D017186:Titrimetry
D000953:Antigens, Protozoan; D001639:Bicarbonates; D050091:Dendrimers; C514457:HRP-2 antigen, Plasmodium falciparum; D006420:Hemeproteins; D015800:Protozoan Proteins; D001224:Aspartic Acid; C020753:hemozoin; D006418:Heme; D001216:Asparagine