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PDBsum entry 6s1v
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References listed in PDB file
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Key reference
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Title
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Comparison of a retroviral protease in monomeric and dimeric states.
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Authors
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S.Wosicki,
M.Gilski,
H.Zabranska,
I.Pichova,
M.Jaskolski.
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Ref.
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Acta Crystallogr D Struct Biol, 2019,
75,
904-917.
[DOI no: ]
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PubMed id
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Abstract
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Retroviral proteases (RPs) are of high interest owing to their crucial role in
the maturation process of retroviral particles. RPs are obligatory homodimers,
with a pepsin-like active site built around two aspartates (in DTG triads) that
activate a water molecule, as the nucleophile, under two flap loops.
Mason-Pfizer monkey virus (M-PMV) is unique among retroviruses as its protease
is also stable in the monomeric form, as confirmed by an existing crystal
structure of a 13 kDa variant of the protein (M-PMV PR) and its previous
biochemical characterization. In the present work, two mutants of M-PMV PR, D26N
and C7A/D26N/C106A, were crystallized in complex with a peptidomimetic inhibitor
and one mutant (D26N) was crystallized without the inhibitor. The crystal
structures were solved at resolutions of 1.6, 1.9 and 2.0 Å, respectively. At
variance with the previous study, all of the new structures have the canonical
dimeric form of retroviral proteases. The protomers within a dimer differ mainly
in the flap-loop region, with the most extreme case observed in the apo
structure, in which one flap loop is well defined while the other flap loop is
not defined by electron density. The presence of the inhibitor molecules in the
complex structures was assessed using polder maps, but some details of their
conformations remain ambiguous. In all of the presented structures the active
site contains a water molecule buried deeply between the Asn26-Thr27-Gly28
triads of the protomers. Such a water molecule is completely unique not only in
retropepsins but also in aspartic proteases in general. The C7A and C106A
mutations do not influence the conformation of the protein. The Cys106 residue
is properly placed at the homodimer interface area for a disulfide cross-link,
but the reducing conditions of the crystallization experiment prevented S-S bond
formation. An animated Interactive 3D Complement (I3DC) is available in
Proteopedia at http://proteopedia.org/w/Journal:Acta_Cryst_D:S2059798319011355.
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Secondary reference #1
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Title
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Crystal structure of a monomeric retroviral protease solved by protein folding game players.
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Authors
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F.Khatib,
F.Dimaio,
S.Cooper,
M.Kazmierczyk,
M.Gilski,
S.Krzywda,
H.Zabranska,
I.Pichova,
J.Thompson,
Z.Popović,
M.Jaskolski,
D.Baker.
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Ref.
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Nat Struct Biol, 2011,
18,
1175-1177.
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PubMed id
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Secondary reference #2
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Title
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High-Resolution structure of a retroviral protease folded as a monomer.
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Authors
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M.Gilski,
M.Kazmierczyk,
S.Krzywda,
H.Zábranská,
S.Cooper,
Z.Popović,
F.Khatib,
F.Dimaio,
J.Thompson,
D.Baker,
I.Pichová,
M.Jaskolski.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2011,
67,
907-914.
[DOI no: ]
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PubMed id
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Secondary reference #3
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Title
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Crystal structure of a retroviral protease proves relationship to aspartic protease family.
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Authors
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M.Miller,
M.Jaskólski,
J.K.Rao,
J.Leis,
A.Wlodawer.
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Ref.
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Nature, 1989,
337,
576-579.
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PubMed id
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Secondary reference #4
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Title
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Conserved folding in retroviral proteases: crystal structure of a synthetic HIV-1 protease.
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Authors
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A.Wlodawer,
M.Miller,
M.Jaskólski,
B.K.Sathyanarayana,
E.Baldwin,
I.T.Weber,
L.M.Selk,
L.Clawson,
J.Schneider,
S.B.Kent.
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Ref.
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Science, 1989,
245,
616-621.
[DOI no: ]
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PubMed id
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