Monkeypox DNA Polymerase: Difference between revisions

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==DNA binding & active site==
==DNA Binding & Active Site==


'''Bound nucleic acids:''' 22-nt template strand + 14-nt primer strand in the structure; incoming dTTP and a catalytic Mg²⁺ are observed.
'''Bound nucleic acids:''' 22-nt template strand + 14-nt primer strand in the structure, incoming dTTP and a catalytic Mg²⁺ are observed.


'''DNA path:''' duplex lies in groove between palm and thumb; single-stranded 5′ template exits through a channel formed by F8 NTD + Exo and E4, perpendicular to the duplex.
'''DNA path:''' duplex lies in groove between palm and thumb. Single-stranded 5′ template exits through a channel formed by F8 NTD + Exo and E4, perpendicular to the duplex.


'''Residues coordinating catalysis / substrate:''' conserved Asp residues D549 (motif A) and D753 (motif C) coordinate the catalytic metal; Y554 stacks the incoming ribose (steric gate against rNTPs); R634 and K661 stabilize triphosphate. These motifs closely mirror canonical B-family polymerases.
'''Residues coordinating catalysis / substrate:''' conserved Asp residues D549 (motif A- F8) and D753 (motif C- A22) coordinate the catalytic metal; Y554 stacks the incoming ribose (steric gate against rNTPs); R634 and K661 stabilize triphosphate. These motifs closely mirror canonical B-family polymerases.
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==Processivity mechanism — “forward sliding clamp”==
==Processivity Mechanism — “forward sliding clamp”==


'''Key observation:''' A22–E4 folds back and, together with F8 NTD/Exo, forms a closed ring/channel that encircles the single-stranded template.
'''Key observation:''' A22–E4 folds back and, together with F8 NTD/Exo, forms a closed ring/channel that encircles the single-stranded template.
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==Notable structural features==
==Significant Structural Features==


Fingers domain rotates (~17°) toward palm in replicating state — brings R634 / K661 closer to incoming dNTP triphosphate.
Fingers domain rotates (~17°) toward palm in replicating state — brings R634 / K661 closer to incoming dNTP triphosphate.


Thumb wraps around duplex; DNA duplex remains B-form over the 14 base pairs modeled.
Thumb wraps around duplex. DNA duplex remains B-form over the 14 base pairs modeled.


A22 Mid domain resembles ligase O-adenylylation/OB modules but substitutions (hydrophobic/negative residues) likely prevent ATP binding — A22 is a degenerative ligase-like linker rather than an active ligase.
A22’s Mid domain resembles ligase folds but has substitutions that likely prevent ATP binding, supporting an inactive structural role.


47 F8 residues directly contact DNA (29 to template strand, 18 to primer strand), mostly interacting with phosphodiester backbone rather than bases — explains sequence-independent elongation.
47 F8 residues directly contact DNA (29 to template strand, 18 to primer strand), mostly interacting with phosphodiester backbone rather than bases — explains sequence-independent elongation.


</StructureSection>
</StructureSection>
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