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PDBsum entry 1at3
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Serine protease
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PDB id
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1at3
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Contents |
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* Residue conservation analysis
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Enzyme class:
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E.C.3.4.21.97
- assemblin.
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Reaction:
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Cleaves -Ala-|-Ser- and -Ala-|-Ala- bonds in the scaffold protein.
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DOI no:
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Biochemistry
36:14023-14029
(1997)
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PubMed id:
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Active site cavity of herpesvirus proteases revealed by the crystal structure of herpes simplex virus protease/inhibitor complex.
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S.S.Hoog,
W.W.Smith,
X.Qiu,
C.A.Janson,
B.Hellmig,
M.S.McQueney,
K.O'Donnell,
D.O'Shannessy,
A.G.DiLella,
C.Debouck,
S.S.Abdel-Meguid.
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ABSTRACT
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Human herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are responsible for
herpes labialis (cold sores) and genital herpes, respectively. They encode a
serine protease that is required for viral replication, and represent a viable
target for therapeutic intervention. Here, we report the crystal structures of
HSV-1 and HSV-2 proteases, the latter in the presence and absence of the
covalently bound transition state analog inhibitor diisopropyl phosphate (DIP).
The HSV-1 and HSV-2 protease structures show a fold that is neither like
chymotrypsin nor like subtilisin, and has been seen only in the recently
determined cytomegalovirus (CMV) and varicella-zoster virus (VZV) protease
structures. HSV-1 and HSV-2 proteases share high sequence homology and have
almost identical three-dimensional structures. However, structural differences
are observed with the less homologous CMV protease, offering a structural basis
for herpes virus protease ligand specificity. The bound inhibitor identifies the
oxyanion hole of these enzymes and defines the active site cavity.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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T.Shahian,
G.M.Lee,
A.Lazic,
L.A.Arnold,
P.Velusamy,
C.M.Roels,
R.K.Guy,
and
C.S.Craik
(2009).
Inhibition of a viral enzyme by a small-molecule dimer disruptor.
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Nat Chem Biol,
5,
640-646.
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A.Lazic,
D.H.Goetz,
A.M.Nomura,
A.B.Marnett,
and
C.S.Craik
(2007).
Substrate modulation of enzyme activity in the herpesvirus protease family.
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J Mol Biol,
373,
913-923.
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PDB code:
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A.C.Steven,
J.B.Heymann,
N.Cheng,
B.L.Trus,
and
J.F.Conway
(2005).
Virus maturation: dynamics and mechanism of a stabilizing structural transition that leads to infectivity.
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Curr Opin Struct Biol,
15,
227-236.
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A.D.Borthwick
(2005).
Design of translactam HCMV protease inhibitors as potent antivirals.
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Med Res Rev,
25,
427-452.
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A.N.Loveland,
C.K.Chan,
E.J.Brignole,
and
W.Gibson
(2005).
Cleavage of human cytomegalovirus protease pUL80a at internal and cryptic sites is not essential but enhances infectivity.
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J Virol,
79,
12961-12968.
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A.B.Marnett,
A.M.Nomura,
N.Shimba,
P.R.Ortiz de Montellano,
and
C.S.Craik
(2004).
Communication between the active sites and dimer interface of a herpesvirus protease revealed by a transition-state inhibitor.
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Proc Natl Acad Sci U S A,
101,
6870-6875.
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J.Liu,
and
A.Mushegian
(2004).
Displacements of prohead protease genes in the late operons of double-stranded-DNA bacteriophages.
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J Bacteriol,
186,
4369-4375.
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N.Shimba,
A.M.Nomura,
A.B.Marnett,
and
C.S.Craik
(2004).
Herpesvirus protease inhibition by dimer disruption.
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J Virol,
78,
6657-6665.
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A.Nayeem,
S.Krystek,
and
T.Stouch
(2003).
An assessment of protein-ligand binding site polarizability.
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Biopolymers,
70,
201-211.
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S.S.Coberley,
R.C.Condit,
L.H.Herbst,
and
P.A.Klein
(2002).
Identification and expression of immunogenic proteins of a disease-associated marine turtle herpesvirus.
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J Virol,
76,
10553-10558.
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T.R.Pray,
K.K.Reiling,
B.G.Demirjian,
and
C.S.Craik
(2002).
Conformational change coupling the dimerization and activation of KSHV protease.
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Biochemistry,
41,
1474-1482.
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M.Matsumoto,
S.Misawa,
N.Chiba,
H.Takaku,
and
H.Hayashi
(2001).
Selective nonpeptidic inhibitors of herpes simplex virus type 1 and human cytomegalovirus proteases.
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Biol Pharm Bull,
24,
236-241.
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R.Batra,
R.Khayat,
and
L.Tong
(2001).
Molecular mechanism for dimerization to regulate the catalytic activity of human cytomegalovirus protease.
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Nat Struct Biol,
8,
810-817.
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PDB codes:
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R.Khayat,
R.Batra,
M.J.Massariol,
L.Lagacé,
and
L.Tong
(2001).
Investigating the role of histidine 157 in the catalytic activity of human cytomegalovirus protease.
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Biochemistry,
40,
6344-6351.
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PDB codes:
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K.K.Reiling,
T.R.Pray,
C.S.Craik,
and
R.M.Stroud
(2000).
Functional consequences of the Kaposi's sarcoma-associated herpesvirus protease structure: regulation of activity and dimerization by conserved structural elements.
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Biochemistry,
39,
12796-12803.
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PDB code:
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N.J.Tigue,
and
J.Kay
(1998).
Autoprocessing and peptide substrates for human herpesvirus 6 proteinase.
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J Biol Chem,
273,
26441-26446.
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P.H.Liang,
K.A.Brun,
J.A.Feild,
K.O'Donnell,
M.L.Doyle,
S.M.Green,
A.E.Baker,
M.N.Blackburn,
and
S.S.Abdel-Meguid
(1998).
Site-directed mutagenesis probing the catalytic role of arginines 165 and 166 of human cytomegalovirus protease.
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Biochemistry,
37,
5923-5929.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
