DNA Polymerase Function and Fidelity Depend on Specific Active-site Interactions and Geometry
In Pol λ,
Mutating Arg517 leads to increased DNA motion and higher deletion error rates MM
dCTP
MM QM
O1A
Potential Energy (kcal/mol)
25 20
DNA Primer
15 10
3.08
O2A 1.96
O3' 2.30
5
QM
dCTP
Potential Energy Profile for the Water-Assisted Deprotonation Pathway in the Optimized Model
Mg2+
Asp105 Mg2+
DNA Primer
O5' O2A O1A 4.72 Wat3 O3' 5.22
30
Mg2+
Wat5Asp105 3.38 Mg2+
0 Reaction Coordinate
Glu106
Potential Energy Profile for the Phosphate-oxygen-Assisted Deprotonation Pathway in the Crystal Model
35
Potential Energy (kcal/mol)
In Dpo4,
25 20 15 10 5 0
Wat4
Reaction Coordinate
Asp7
Asp7 Glu106
Optimized Geometry
Less Ideal Geometry
Active site organization affects chemical reaction pathways and associated energy barriers
