Table 2 E9 drug-resistant and temperature-sensitive mutants

Phe171Ser

VACV

araC^r, araA^r, aph^hs (when combined with mutant Cys356Tyr or Gly372Asp or Gly380Ser)

Yellow

Modification of 3′-nucleotide binding at exonuclease site

²¹

ΔLys174

VACV

CDV^r

Yellow

Modification of 3′-nucleotide binding at exonuclease site

²⁰

His185Tyr

VACV

ts Dts83

Black

Destabilization of the exonuclease domain

⁶⁷

Ala314Thr/Val

VACV, CMLV^a, MPV^b

CDV^r and cross-resistance to other nucleoside phosphonate drugs. Stronger drug-resistance together with mutation Ala684Val. PAA^hs

Orange

Mutation in beta-hairpin; may modulate guidance from elongation to editing mode

^{20,22,23,24,25,26}

Ser338Phe

VACV

CDV^r

Orange

Indirect effect on complementary strand binding or strand switching between elongation and editing mode?

²⁵

Cys356Tyr

VACV

PAA^r, aph^hs

Green

Effect on insert 2–finger interaction?

²¹

Gly372Asp

VACV

PAA^r, aph^hs

Green

Effect on insert 2–finger interaction?

²¹

Gly380Ser

VACV

PAA^r, aph^hs

Green

Effect on insert 2–finger interaction?

²¹

Gly392Asp

VACV

ts NG26

Black

Destabilization of insert 2

^21,68

Ala498Thr/Val

VACV

aph^r, PAA^hs, araC^hs, araA^hs

Red

Interference with the rotation of a base in the template required for aph binding

²⁷

Glu611Lys

VACV

ts Cts42

Black

Destabilization of insert 3 or of the elongation site

⁶⁸

Leu670Met

VACV

aph^r

Red

Indirect effect on the binding of the template backbone next to aph-binding site

⁴⁴

Ala684Val/Thr

VACV, CMLV^a, MPV^b

CDV^r and cross-resistance to other nucleoside phosphonate drugs. Stronger drug-resistance together with mutation Ala314Thr

Red

Indirect effect on the binding of the template backbone in the elongation site

^22,23,24,26

Ser686Asn

VACV

ts, Dts20

Black

Destabilization of insert 3 or of the elongation site

⁶⁷

Thr688Ala

VACV

CDV^r and cross-resistance to other nucleoside phosphonate drugs when associated with Ala314Thr mutation. PAA^hs, araC^hs

Red

Indirect effect on template backbone binding in the elongation site

²²

Thr831Ile

VACV

CDV^r and cross-resistance to other nucleoside phosphonate drugs

Pink

Modulation of domain movements by a modification at the thumb–palm domain connection and a changed interaction with the complementary strand

²⁴

Ser851Tyr

VACV

CDV^r and cross-resistance to other nucleoside phosphonate drugs when combined with Ala684Val mutation

Pink

Modulation of domain movements by a modification of the thumb–palm domain interface

²³