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PDBsum entry 2f64
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* Residue conservation analysis
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Enzyme class:
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E.C.2.4.2.6
- nucleoside deoxyribosyltransferase.
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Reaction:
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2-deoxy-D-ribosyl-base1 + base2 = 2-deoxy-D-ribosyl-base2 + base1
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2-deoxy-D-ribosyl-base(1)
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+
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base(2)
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=
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2-deoxy-D-ribosyl-base(2)
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+
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base(1)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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J Med Chem
49:5939-5946
(2006)
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PubMed id:
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Using fragment cocktail crystallography to assist inhibitor design of Trypanosoma brucei nucleoside 2-deoxyribosyltransferase.
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J.Bosch,
M.A.Robien,
C.Mehlin,
E.Boni,
A.Riechers,
F.S.Buckner,
W.C.Van Voorhis,
P.J.Myler,
E.A.Worthey,
G.DeTitta,
J.R.Luft,
A.Lauricella,
S.Gulde,
L.A.Anderson,
O.Kalyuzhniy,
H.M.Neely,
J.Ross,
T.N.Earnest,
M.Soltis,
L.Schoenfeld,
F.Zucker,
E.A.Merritt,
E.Fan,
C.L.Verlinde,
W.G.Hol.
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ABSTRACT
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The 1.8 A resolution de novo structure of nucleoside 2-deoxyribosyltransferase
(EC 2.4.2.6) from Trypanosoma brucei (TbNDRT) has been determined by SADa
phasing in an unliganded state and several ligand-bound states. This enzyme is
important in the salvage pathway of nucleoside recycling. To identify novel lead
compounds, we exploited "fragment cocktail soaks". Out of 304 compounds tried in
31 cocktails, four compounds could be identified crystallographically in the
active site. In addition, we demonstrated that very short soaks of approximately
10 s are sufficient even for rather hydrophobic ligands to bind in the active
site groove, which is promising for the application of similar soaking
experiments to less robust crystals of other proteins.
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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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C.W.Murray,
and
T.L.Blundell
(2010).
Structural biology in fragment-based drug design.
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Curr Opin Struct Biol,
20,
497-507.
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J.Fernández-Lucas,
C.Acebal,
J.V.Sinisterra,
M.Arroyo,
and
I.de la Mata
(2010).
Lactobacillus reuteri 2'-deoxyribosyltransferase, a novel biocatalyst for tailoring of nucleosides.
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Appl Environ Microbiol,
76,
1462-1470.
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J.R.Luft,
N.M.Furlani,
R.E.Nemoyer,
E.J.Penna,
J.R.Wolfley,
M.E.Snell,
S.A.Potter,
and
E.H.Snell
(2010).
Crystal cookery - using high-throughput technologies and the grocery store as a teaching tool.
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J Appl Crystallogr,
43,
1189-1207.
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N.Drinkwater,
H.Vu,
K.M.Lovell,
K.R.Criscione,
B.M.Collins,
T.E.Prisinzano,
S.A.Poulsen,
M.J.McLeish,
G.L.Grunewald,
and
J.L.Martin
(2010).
Fragment-based screening by X-ray crystallography, MS and isothermal titration calorimetry to identify PNMT (phenylethanolamine N-methyltransferase) inhibitors.
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Biochem J,
431,
51-61.
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PDB codes:
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C.L.Verlinde,
E.Fan,
S.Shibata,
Z.Zhang,
Z.Sun,
W.Deng,
J.Ross,
J.Kim,
L.Xiao,
T.L.Arakaki,
J.Bosch,
J.M.Caruthers,
E.T.Larson,
I.Letrong,
A.Napuli,
A.Kelly,
N.Mueller,
F.Zucker,
W.C.Van Voorhis,
E.A.Merritt,
and
W.G.Hol
(2009).
Fragment-based cocktail crystallography by the medical structural genomics of pathogenic protozoa consortium.
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Curr Top Med Chem,
9,
1678-1687.
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D.R.Davies,
B.Mamat,
O.T.Magnusson,
J.Christensen,
M.H.Haraldsson,
R.Mishra,
B.Pease,
E.Hansen,
J.Singh,
D.Zembower,
H.Kim,
A.S.Kiselyov,
A.B.Burgin,
M.E.Gurney,
and
L.J.Stewart
(2009).
Discovery of leukotriene A4 hydrolase inhibitors using metabolomics biased fragment crystallography.
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J Med Chem,
52,
4694-4715.
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PDB codes:
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W.C.Van Voorhis,
W.G.Hol,
P.J.Myler,
and
L.J.Stewart
(2009).
The role of medical structural genomics in discovering new drugs for infectious diseases.
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PLoS Comput Biol,
5,
e1000530.
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PDB codes:
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J.D.Bauman,
K.Das,
W.C.Ho,
M.Baweja,
D.M.Himmel,
A.D.Clark,
D.A.Oren,
P.L.Boyer,
S.H.Hughes,
A.J.Shatkin,
and
E.Arnold
(2008).
Crystal engineering of HIV-1 reverse transcriptase for structure-based drug design.
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Nucleic Acids Res,
36,
5083-5092.
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PDB code:
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J.Weigelt,
L.D.McBroom-Cerajewski,
M.Schapira,
Y.Zhao,
C.H.Arrowsmith,
and
C.H.Arrowmsmith
(2008).
Structural genomics and drug discovery: all in the family.
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Curr Opin Chem Biol,
12,
32-39.
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K.U.Wendt,
M.S.Weiss,
P.Cramer,
and
D.W.Heinz
(2008).
Structures and diseases.
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Nat Struct Mol Biol,
15,
117-120.
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P.A.Kaminski,
P.Dacher,
L.Dugué,
and
S.Pochet
(2008).
In vivo reshaping the catalytic site of nucleoside 2'-deoxyribosyltransferase for dideoxy- and didehydronucleosides via a single amino acid substitution.
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J Biol Chem,
283,
20053-20059.
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H.Jhoti,
A.Cleasby,
M.Verdonk,
and
G.Williams
(2007).
Fragment-based screening using X-ray crystallography and NMR spectroscopy.
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Curr Opin Chem Biol,
11,
485-493.
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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
codes are
shown on the right.
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Links
