02684nas a2200265   4500000000100000008004100001653001200042653001500054653001200069653001600081653001400097100001200111700001800123700001300141700001600154700001100170700001300181700001300194245012000207856011600327300001300443490000600456520194200462022001402404       2015                            d10aleprosy10aBiomarkers10aAntigen10aChaperonins10aTreatment1 aNandi S1 aChakraborty A1 aPanda AK1 aSinha Ray S1 aKar RK1 aBhunia A1 aBiswas A00aInteraction of ATP with a Small Heat Shock Protein from Mycobacterium leprae: Effect on Its Structure and Function.  uhttp://www.plosntds.org/article/fetchObject.action?uri=info:doi/10.1371/journal.pntd.0003661&representation=PDF  ae00036610 v93 a<p>Adenosine-5'-triphosphate (ATP) is an important phosphate metabolite abundantly found in Mycobacterium leprae bacilli. This pathogen does not derive ATP from its host but has its own mechanism for the generation of ATP. Interestingly, this molecule as well as several antigenic proteins act as bio-markers for the detection of leprosy. One such bio-marker is the 18 kDa antigen. This 18 kDa antigen is a small heat shock protein (HSP18) whose molecular chaperone function is believed to help in the growth and survival of the pathogen. But, no evidences of interaction of ATP with HSP18 and its effect on the structure and chaperone function of HSP18 are available in the literature. Here, we report for the first time evidences of "HSP18-ATP" interaction and its consequences on the structure and chaperone function of HSP18. TNP-ATP binding experiment and surface plasmon resonance measurement showed that HSP18 interacts with ATP with a sub-micromolar binding affinity. Comparative sequence alignment between M. leprae HSP18 and αB-crystallin identified the sequence 49KADSLDIDIE58 of HSP18 as the Walker-B ATP binding motif. Molecular docking studies revealed that β4-β8 groove/strands as an ATP interactive region in M. leprae HSP18. ATP perturbs the tertiary structure of HSP18 mildly and makes it less susceptible towards tryptic cleavage. ATP triggers exposure of additional hydrophobic patches at the surface of HSP18 and induces more stability against chemical and thermal denaturation. In vitro aggregation and thermal inactivation assays clearly revealed that ATP enhances the chaperone function of HSP18. Our studies also revealed that the alteration in the chaperone function of HSP18 is reversible and is independent of ATP hydrolysis. As the availability and binding of ATP to HSP18 regulates its chaperone function, this functional inflection may play an important role in the survival of M. leprae in hosts.</p>
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