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PDBsum entry 1qxy
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* Residue conservation analysis
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Enzyme class:
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E.C.3.4.11.18
- methionyl aminopeptidase.
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Reaction:
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Release of N-terminal amino acids, preferentially methionine, from peptides and arylamides.
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Cofactor:
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Cobalt cation
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DOI no:
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J Med Chem
47:1325-1328
(2004)
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PubMed id:
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Crystal structures of Staphylococcusaureus methionine aminopeptidase complexed with keto heterocycle and aminoketone inhibitors reveal the formation of a tetrahedral intermediate.
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A.Douangamath,
G.E.Dale,
A.D'Arcy,
M.Almstetter,
R.Eckl,
A.Frutos-Hoener,
B.Henkel,
K.Illgen,
S.Nerdinger,
H.Schulz,
A.Mac Sweeney,
A.MacSweeney,
M.Thormann,
A.Treml,
S.Pierau,
S.Wadman,
C.Oefner.
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ABSTRACT
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High-resolution crystal structures of Staphylococcus aureus methionine
aminopeptidase I in complex with various keto heterocycles and aminoketones were
determined, and the intermolecular ligand interactions with the enzyme are
reported. The compounds are effective inhibitors of the S. aureus enzyme because
of the formation of an uncleavable tetrahedral intermediate upon binding. The
electron densities unequivocally show the enzyme-catalyzed transition-state
analogue mimicking that for amide bond hydrolysis of substrates.
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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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J.P.Lu,
and
Q.Z.Ye
(2010).
Expression and characterization of Mycobacterium tuberculosis methionine aminopeptidase type 1a.
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Bioorg Med Chem Lett,
20,
2776-2779.
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J.P.Lu,
S.C.Chai,
and
Q.Z.Ye
(2010).
Catalysis and inhibition of Mycobacterium tuberculosis methionine aminopeptidase.
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J Med Chem,
53,
1329-1337.
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PDB codes:
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S.C.Chai,
and
Q.Z.Ye
(2010).
A cell-based assay that targets methionine aminopeptidase in a physiologically relevant environment.
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Bioorg Med Chem Lett,
20,
2129-2132.
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S.C.Chai,
and
Q.Z.Ye
(2009).
Metal-mediated inhibition is a viable approach for inhibiting cellular methionine aminopeptidase.
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Bioorg Med Chem Lett,
19,
6862-6864.
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S.Mitra,
B.Bennett,
and
R.C.Holz
(2009).
Mutation of H63 and its catalytic affect on the methionine aminopeptidase from Escherichia coli.
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Biochim Biophys Acta,
1794,
137-143.
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S.Mitra,
G.Sheppard,
J.Wang,
B.Bennett,
and
R.C.Holz
(2009).
Analyzing the binding of Co(II)-specific inhibitors to the methionyl aminopeptidases from Escherichia coli and Pyrococcus furiosus.
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J Biol Inorg Chem,
14,
573-585.
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H.Li,
H.Yang,
and
L.S.Liebeskind
(2008).
Synthesis of high enantiopurity N-protected alpha-amino ketones by thiol ester-organostannane cross-coupling using pH-neutral conditions.
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Org Lett,
10,
4375-4378.
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S.C.Chai,
W.L.Wang,
and
Q.Z.Ye
(2008).
FE(II) Is the Native Cofactor for Escherichia coli Methionine Aminopeptidase.
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J Biol Chem,
283,
26879-26885.
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S.J.Watterson,
S.Mitra,
S.I.Swierczek,
B.Bennett,
and
R.C.Holz
(2008).
Kinetic and spectroscopic analysis of the catalytic role of H79 in the methionine aminopeptidase from Escherichia coli.
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Biochemistry,
47,
11885-11893.
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S.Mitra,
K.M.Job,
L.Meng,
B.Bennett,
and
R.C.Holz
(2008).
Analyzing the catalytic role of Asp97 in the methionine aminopeptidase from Escherichia coli.
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FEBS J,
275,
6248-6259.
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W.L.Wang,
S.C.Chai,
M.Huang,
H.Z.He,
T.D.Hurley,
and
Q.Z.Ye
(2008).
Discovery of inhibitors of Escherichia coli methionine aminopeptidase with the Fe(II)-form selectivity and antibacterial activity.
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J Med Chem,
51,
6110-6120.
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PDB code:
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M.Huang,
S.X.Xie,
Z.Q.Ma,
Q.Q.Huang,
F.J.Nan,
and
Q.Z.Ye
(2007).
Inhibition of monometalated methionine aminopeptidase: inhibitor discovery and crystallographic analysis.
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J Med Chem,
50,
5735-5742.
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PDB codes:
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Z.Q.Ma,
S.X.Xie,
Q.Q.Huang,
F.J.Nan,
T.D.Hurley,
and
Q.Z.Ye
(2007).
Structural analysis of inhibition of E. coli methionine aminopeptidase: implication of loop adaptability in selective inhibition of bacterial enzymes.
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BMC Struct Biol,
7,
84.
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PDB codes:
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Q.Z.Ye,
S.X.Xie,
Z.Q.Ma,
M.Huang,
and
R.P.Hanzlik
(2006).
Structural basis of catalysis by monometalated methionine aminopeptidase.
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Proc Natl Acad Sci U S A,
103,
9470-9475.
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PDB codes:
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S.X.Xie,
W.J.Huang,
Z.Q.Ma,
M.Huang,
R.P.Hanzlik,
and
Q.Z.Ye
(2006).
Structural analysis of metalloform-selective inhibition of methionine aminopeptidase.
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Acta Crystallogr D Biol Crystallogr,
62,
425-432.
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PDB codes:
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X.Hu,
A.Addlagatta,
B.W.Matthews,
and
J.O.Liu
(2006).
Identification of pyridinylpyrimidines as inhibitors of human methionine aminopeptidases.
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Angew Chem Int Ed Engl,
45,
3772-3775.
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PDB code:
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R.Schiffmann,
A.Heine,
G.Klebe,
and
C.D.Klein
(2005).
Metal ions as cofactors for the binding of inhibitors to methionine aminopeptidase: a critical view of the relevance of in vitro metalloenzyme assays.
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Angew Chem Int Ed Engl,
44,
3620-3623.
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PDB code:
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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
