Unusual weak and delayed GTPase activity of FtsZ from human pathogenic bacteria Helicobacter pylori

Abstract

Abstract Actively treadmilling FtsZ acts as the pivotal scaffold for bacterial cell divisome components, providing them with a circumferential ride along the site of future division. FtsZ from slow-growing Helicobacter pylori (HpFtsZ), a class I carcinogen that thrives abundantly in the acidic environment, is poorly understood. We studied HpFtsZ as a function of pH, cations and time and compared it with well-studied Escherichia coli FtsZ (EcFtsZ). HpFtsZ shows pH-dependent GTPase activity, which is inhibited under acidic conditions. Mg+2 ions play an indispensable role in its GTPase activity; however, higher Mg+2 levels negatively affect its activity. As compared to EcFtsZ, HpFtsZ exhibits lower and slower nucleotide hydrolysing activity. Molecular dynamics simulation studies of FtsZ reveal that GTP binding induces a rewiring of the hydrogen bond network, which results in reduction of the binding cleft volume leading to the spontaneous release of GTP. The GTPase activity is linked to the extent of reduction in the binding cleft volume, which is also supported by the binding free energy analysis. Evidently, HpFtsZ is a pH-sensitive GTPase with low efficiency that may reflect on the overall slow growth rate of H. pylori.