Three different mutations in the DNA topoisomerase 1B in Leishmania infantum contribute to resistance to antitumor drug topotecan

Table 2 Analysis of the hydrogen bond network in covalent complex simulations

	WT	F187Y	G191A	W232R
Active site pentad and surrounding residues
ARG314:PTR222s	97.78	98.26	97.97	98.82
CYS329:ARG314	98.46	98.33	98.38	98.12
LYS352:ASP353	60.41
ILE355:LYS352	78.65	77.83	78.79	86.33
ARG410:ALA406	44.55
ARG410:PTR222s	99.72	99.79	99.67	99.55
ARG410:ALA312	85.33	97.66	91.83	97.50
ARG410:CYS451		41.72		48.01
ALA414:ARG410	90.37	90.21	85.86	89.70
HIS453:ALA202s	85.22	82.20	82.39	80.23
HIS453:PTR222s	97.64	90.28	96.79	90.86
SER214s:HIS453	93.57	93.87	87.36	92.65
PTR222s:SER218s	76.09	65.74	66.94	67.68
Residues of point mutations and surrounding residues
PHE(Y)187:LYS198	99.05	99.37	99.40	99.53
GLY189:PHE(Y)187		80.85	69.95	64.26
GLY197:PHE187	93.63	99.31	99.53	99.56
HIS193:GLY(A)191		65.35		65.47
TRP(R)242:LYS225	96.20	84.25	98.36	95.50

Percentage of the hydrogen bonds established by the active site pentad with the surrounding residues (PTR stands for phosphotyrosine, while “s” following the residue number indicates that residue belongs to the small subunit)

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