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PDBsum entry 1dml
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DNA binding protein/transferase
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PDB id
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1dml
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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The crystal structure of an unusual processivity factor, Herpes simplex virus ul42, Bound to the c terminus of its cognate polymerase.
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Authors
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H.J.Zuccola,
D.J.Filman,
D.M.Coen,
J.M.Hogle.
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Ref.
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Mol Cell, 2000,
5,
267-278.
[DOI no: ]
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PubMed id
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Abstract
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Herpes simplex virus DNA polymerase is a heterodimer composed of a catalytic
subunit, Pol, and an unusual processivity subunit, UL42, which, unlike
processivity factors such as PCNA, directly binds DNA. The crystal structure of
a complex of the C-terminal 36 residues of Pol bound to residues 1-319 of UL42
reveals remarkable similarities between UL42 and PCNA despite contrasting
biochemical properties and lack of sequence homology. Moreover, the Pol-UL42
interaction resembles the interaction between the cell cycle regulator p21 and
PCNA. The structure and previous data suggest that the UL42 monomer interacts
with DNA quite differently than does multimeric toroidal PCNA. The details of
the structure lead to a model for the mechanism of UL42, provide the basis for
drug design, and allow modeling of other proteins that lack sequence homology
with UL42 or PCNA.
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Figure 4.
Figure 4. Interaction of the Pol Peptide with UL42The
peptide is folded into an αβα structure on the front surface
of UL42. (A) Ribbon diagram of UL42 (blue) bound to peptide A
(orange) (UL42 is oriented as in Figure 2). (B) Molecular
surface representation of UL42 with peptide A bound. P1 and P2
denote pockets formed on the surface of the molecule. Labeled
residues belong to the peptide, except for that of UL42 Q171,
which is labeled as a projection on the surface. The side chains
of the peptide are colored as follows: blue, K, R, and H; red, D
and E; yellow, G; magenta, A; cyan, T; and white, L, V, and F.
(C) Schematic representation of the intermolecular hydrogen
bonds between the peptide (orange) and UL42 (blue). Spheres
represent the alpha carbons. The cylinders represent the two
helices of the peptide, and the arrows indicate the region of
Pol and UL42 that form the antiparallel β strands.
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Figure 7.
Figure 7. Regions of Other Herpesvirus Polymerase Accessory
Proteins Predicted to Have PCNA/UL42-like StructuresThe UCLA-DOE
fold recognition server at http://fold.doe-mbi.ucla.edu was sent
the sequences of human cytomegalovirus (HCMV) UL44, human
herpesvirus-6 (HHV-6) p41, Kaposi sarcoma–associated
herpesvirus (human herpesvirus-8, HHV-8) PF-8, and Epstein-Barr
virus (EBV) BMRF1. HCMV and HHV-6 are β herpesviruses, and EBV
and HHV-8 are γ herpesviruses.
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The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2000,
5,
267-278)
copyright 2000.
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