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

Table 3 Analysis of the hydrogen bond network in non-covalent complex simulations

	WT	F187Y	G191A	W232R
Active site pentad and surrounding residues and DNA bases
ARG314:ASN452			69.42
CYS329: ARG314	98.76	97.96	98.37	97.98
LYS352:ASP353	70.96	68.41	88.26
ILE355:LYS352	57.14	73.93	96.42	75.04
ARG410:ALA406	44.32	61.96	97.86
ARG410:ALA312	90.58	98.60	75.04	90.59
ARG410:TYR222s	59.80	83.62
ARG410:CYS451		45.97
ALA414:ARG410	89.56	89.25	96.27	90.98
HIS453:ALA202s	79.59	85.58	90.06	86.04
SER214s:HIS453	85.85	93.02	76.47	88.41
TYR222s:SER218s	68.45	73.21	78.77	64.46
ARG314:THY +1	87.60	98.50	73.82	88.02
LYS352:THY −1		52.21	68.58	53.88
LYS352:THY +1				74.12
ARG410:THY +1	75.18	86.34
HIS453:THY +1	94.79	96.96	55.49	87.59
TYR222s:THY −1	65.22	80.60		43.97
TYR222s:THY +1	55.33			70.77
Residues of point mutations and surrounding residues
PHE(Y)187:LYS198	99.25	99.14	99.33	99.48
GLY189:PHE(Y)187				44.74
GLY197:PHE187	92.48	99.16	99.29	99.52
HIS193:GLY(A)191			46.89	61.69
TRP(R)242:LYS225	98.45	98.33	98.03	94.67
TRP(R)242:LYS182				73.40

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

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