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References listed in PDB file
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Key reference
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Title
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Complex of n-Phosphonacetyl-L-Aspartate with aspartate carbamoyltransferase. X-Ray refinement, Analysis of conformational changes and catalytic and allosteric mechanisms.
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Authors
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H.M.Ke,
W.N.Lipscomb,
Y.J.Cho,
R.B.Honzatko.
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Ref.
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J Mol Biol, 1988,
204,
725-747.
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PubMed id
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Abstract
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The allosteric enzyme aspartate carbamoyltransferase of Escherichia coli
consists of six regulatory chains (R) and six catalytic chains (C) in D3
symmetry. The less active T conformation, complexed to the allosteric inhibitor
CTP has been refined to 2.6 A (R-factor of 0.155). We now report refinement of
the more active R conformation, complexed to the bisubstrate analog
N-phosphonacetyl-L-aspartate (PALA) to 2.4 A (R-factor of 0.165,
root-mean-square deviations from ideal bond distances and angles of 0.013 A and
2.2 degrees, respectively). The antiparallel beta-sheet in the revised segment
8-65 of the regulatory chain of the T conformation is confirmed in the R
conformation, as is also the interchange of alanine 1 with the side-chain of
asparagine 2 in the catalytic chain. The crystallographic asymmetric unit
containing one-third of the molecule (C2R2) includes 925 sites for water
molecules, and seven side-chains in alternative conformations. The gross
conformational changes of the T to R transition are confirmed, including the
elongation of the molecule along its threefold axis by 12 A, the relative
reorientation of the catalytic trimers C3 by 10 degrees, and the rotation of the
regulatory dimers R2 about the molecular twofold axis by 15 degrees. No changes
occur in secondary structure. Essentially rigid-body transformations account for
the movement of the four domains of each catalytic-regulatory unit; these
include the allosteric effector domain, the equatorial (aspartate) domain, and
the combination of the polar (carbamyl phosphate) and zinc domain, which moves
as a rigid unit. However, interfaces change, for example the interface between
the zinc domain of the R chain and the equatorial domain of the C chain, is
nearly absent in the T state, but becomes extensive in the R state of the
enzyme; also one catalytic-regulatory interface (C1-R4) of the T state
disappears in the more active R state of the enzyme. Segments 50-55, 77-86 and
231-246 of the catalytic chain and segments 51-55, 67-72 and 150-153 of the
regulatory chain show conformational changes that go beyond the rigid-body
movement of their corresponding domains. The localized conformational changes in
the catalytic chain all derive from the interactions of the enzyme with the
inhibitor PALA; these changes may be important for the catalytic mechanism. The
conformation changes in segments 67-72 and 150-153 of the regulatory chain may
be important for the allosteric control of substrate binding. On the basis of
the conformational differences of the T and R states of the enzyme, we present a
plausible scheme for catalysis that assumes the ordered binding of substrates
and the ordered release o
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Secondary reference #1
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Title
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Structural consequences of effector binding to the t state of aspartate carbamoyltransferase: crystal structures of the unligated and ATP- And ctp-Complexed enzymes at 2.6-A resolution.
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Authors
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R.C.Stevens,
J.E.Gouaux,
W.N.Lipscomb.
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Ref.
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Biochemistry, 1990,
29,
7691-7701.
[DOI no: ]
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PubMed id
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Secondary reference #2
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Title
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Crystal structures of aspartate carbamoyltransferase ligated with phosphonoacetamide, Malonate, And ctp or ATP at 2.8-A resolution and neutral ph.
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Authors
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J.E.Gouaux,
R.C.Stevens,
W.N.Lipscomb.
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Ref.
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Biochemistry, 1990,
29,
7702-7715.
[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 structures of phosphonoacetamide ligated t and phosphonoacetamide and malonate ligated r states of aspartate carbamoyltransferase at 2.8-A resolution and neutral ph.
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Authors
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J.E.Gouaux,
W.N.Lipscomb.
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Ref.
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Biochemistry, 1990,
29,
389-402.
[DOI no: ]
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PubMed id
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Secondary reference #4
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Title
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Structural transitions in crystals of native aspartate carbamoyltransferase.
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Authors
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J.E.Gouaux,
W.N.Lipscomb.
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Ref.
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Proc Natl Acad Sci U S A, 1989,
86,
845-848.
[DOI no: ]
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PubMed id
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Secondary reference #5
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Title
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Structure of a single amino acid mutant of aspartate carbamoyltransferase at 2.5-A resolution: implications for the cooperative mechanism.
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Authors
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J.E.Gouaux,
W.N.Lipscomb,
S.A.Middleton,
E.R.Kantrowitz.
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Ref.
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Biochemistry, 1989,
28,
1798-1803.
[DOI no: ]
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PubMed id
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Secondary reference #6
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Title
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Escherichia coli aspartate transcarbamylase: the relation between structure and function.
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Authors
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E.R.Kantrowitz,
W.N.Lipscomb.
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Ref.
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Science, 1988,
241,
669-674.
[DOI no: ]
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PubMed id
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Secondary reference #7
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Title
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Three-Dimensional structure of carbamoyl phosphate and succinate bound to aspartate carbamoyltransferase.
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Authors
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J.E.Gouaux,
W.N.Lipscomb.
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Ref.
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Proc Natl Acad Sci U S A, 1988,
85,
4205-4208.
[DOI no: ]
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PubMed id
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Secondary reference #8
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Title
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Structural asymmetry in the ctp-Liganded form of aspartate carbamoyltransferase from escherichia coli.
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Authors
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K.H.Kim,
Z.X.Pan,
R.B.Honzatko,
H.M.Ke,
W.N.Lipscomb.
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Ref.
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J Mol Biol, 1987,
196,
853-875.
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PubMed id
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Secondary reference #9
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Title
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2.5 a structure of aspartate carbamoyltransferase complexed with the bisubstrate analog n-(Phosphonacetyl)-L-Aspartate.
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Authors
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K.L.Krause,
K.W.Volz,
W.N.Lipscomb.
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Ref.
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J Mol Biol, 1987,
193,
527-553.
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PubMed id
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Secondary reference #10
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Title
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The catalytic mechanism of escherichia coli aspartate carbamoyltransferase: a molecular modelling study.
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Authors
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J.E.Gouaux,
K.L.Krause,
W.N.Lipscomb.
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Ref.
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Biochem Biophys Res Commun, 1987,
142,
893-897.
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PubMed id
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Secondary reference #11
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Title
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Structure at 2.9-A resolution of aspartate carbamoyltransferase complexed with the bisubstrate analogue n-(Phosphonacetyl)-L-Aspartate.
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Authors
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K.L.Krause,
K.W.Volz,
W.N.Lipscomb.
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Ref.
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Proc Natl Acad Sci U S A, 1985,
82,
1643-1647.
[DOI no: ]
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PubMed id
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Secondary reference #12
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Title
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Structure of unligated aspartate carbamoyltransferase of escherichia coli at 2.6-A resolution.
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Authors
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H.M.Ke,
R.B.Honzatko,
W.N.Lipscomb.
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Ref.
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Proc Natl Acad Sci U S A, 1984,
81,
4037-4040.
[DOI no: ]
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PubMed id
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Secondary reference #13
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Title
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Crystal and molecular structures of native and ctp-Liganded aspartate carbamoyltransferase from escherichia coli.
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Authors
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R.B.Honzatko,
J.L.Crawford,
H.L.Monaco,
J.E.Ladner,
B.F.Ewards,
D.R.Evans,
S.G.Warren,
D.C.Wiley,
R.C.Ladner,
W.N.Lipscomb.
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Ref.
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J Mol Biol, 1982,
160,
219-263.
[DOI no: ]
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PubMed id
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Figure 3.
FIG:. . Variation ofthtl crystallographic -factor with wsolution fi)r the 1132 (0) and 1'311 (m) rystal
forms. )ata ww grouped ccording o resolution in 20 hells venly spaced in limits of sine theta. The
solid inw rcpresrnt he t~hrorrtical variaton of th factor at he, sprcified co-ordiate error r.m.s.).
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Figure 10.
FIN: 10. Intrrfam betw-een catalytic chair) Cl (unbroken inrs) and rrgulatory and catalytic: chains H4
and 4 broken lines). Cl cont.rihutes Clu238 o a polar link ith Tyrl65 of C4. and thr tmrklwnr of
Ala237 and ys236 f Cl ink to Asp111 f R4.
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The above figures are
reproduced from the cited reference
with permission from Elsevier
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Secondary reference #14
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Title
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Interactions of phosphate ligands with escherichia coli aspartate carbamoyltransferase in the crystalline state.
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Authors
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R.B.Honzatko,
W.N.Lipscomb.
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Ref.
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J Mol Biol, 1982,
160,
265-286.
[DOI no: ]
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PubMed id
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Figure 1.
FIG. 1. ic drawing f egulator~~oatal?;tic unit of aspartate carbano?-ltranf'ernse. hobvirlg
vir down the ole~wlar -fold axis rom the outside f he molrwle. Helicrs are shown as ylindrrs
nd strands of p-stucture as arrows. The phosphate crevice is he cleft between he 2 omains of the-
atalytic chain. Arginine residues 54. 05 and 67. which ind hosphate ligands. comr from helix HZ.
trand 84 and heli H6, respectively. The allosteric site for nucleotidrs is in a pocket of the
allosteric ffector domain. Residues that ind he base f wlroside triphosphatw riginate rom he S-
t,rrminal trand, and residues that are ear thr triphosphatc estw moiety rr a part of thr loo;)
crmnrcting strands S2' o X3'.
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The above figure is
reproduced from the cited reference
with permission from Elsevier
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Secondary reference #15
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Title
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Interactions of metal-Nucleotide complexes with aspartate carbamoyltransferase in the crystalline state.
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Authors
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R.B.Honzatko,
W.N.Lipscomb.
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Ref.
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Proc Natl Acad Sci U S A, 1982,
79,
7171-7174.
[DOI no: ]
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PubMed id
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Secondary reference #16
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Title
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Gross quaternary changes in aspartate carbamoyltransferase are induced by the binding of n-(Phosphonacetyl)-L-Aspartate: a 3.5-A resolution study.
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Authors
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J.E.Ladner,
J.P.Kitchell,
R.B.Honzatko,
H.M.Ke,
K.W.Volz,
A.J.Kalb,
R.C.Ladner,
W.N.Lipscomb.
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Ref.
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Proc Natl Acad Sci U S A, 1982,
79,
3125-3128.
[DOI no: ]
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PubMed id
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Secondary reference #17
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Title
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A 3.0-A resolution study of nucleotide complexes with aspartate carbamoyltransferase.
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Authors
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R.B.Honzatko,
H.L.Monaco,
W.N.Lipscomb.
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Ref.
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Proc Natl Acad Sci U S A, 1979,
76,
5105-5109.
[DOI no: ]
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PubMed id
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Secondary reference #18
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Title
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Three-Dimensional structures of aspartate carbamoyltransferase from escherichia coli and of its complex with cytidine triphosphate.
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Authors
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H.L.Monaco,
J.L.Crawford,
W.N.Lipscomb.
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Ref.
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Proc Natl Acad Sci U S A, 1978,
75,
5276-5280.
[DOI no: ]
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PubMed id
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Secondary reference #19
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Title
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Binding site at 5.5 angstroms resolution of cytidine triphosphate, The allosteric inhibitor of aspartate transcarbamylase from escherichia coli. Relation to mechanisms of control
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Authors
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W.N.Lipscomb,
B.F.P.Edwards,
D.R.Evans,
S.C.Pastra-Landis.
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Ref.
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structure and conformation ...
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Secondary reference #20
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Title
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Aspartate transcarbamoylase from escherichia coli: electron density at 5.5 a resolution.
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Authors
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S.G.Warren,
B.F.Edwards,
D.R.Evans,
D.C.Wiley,
W.N.Lipscomb.
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Ref.
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Proc Natl Acad Sci U S A, 1973,
70,
1117-1121.
[DOI no: ]
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PubMed id
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