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* Residue conservation analysis
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Enzyme class:
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E.C.3.1.3.48
- Protein-tyrosine-phosphatase.
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Reaction:
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Protein tyrosine phosphate + H2O = protein tyrosine + phosphate
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Protein tyrosine phosphate
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+
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H(2)O
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=
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protein tyrosine
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+
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phosphate
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Gene Ontology (GO) functional annotation
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Cellular component
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extracellular region
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4 terms
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Biological process
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pathogenesis
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4 terms
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Biochemical function
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protein binding
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5 terms
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DOI no:
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J Bacteriol
187:2175-2181
(2005)
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PubMed id:
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Crystal structure of low-molecular-weight protein tyrosine phosphatase from Mycobacterium tuberculosis at 1.9-A resolution.
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C.Madhurantakam,
E.Rajakumara,
P.A.Mazumdar,
B.Saha,
D.Mitra,
H.G.Wiker,
R.Sankaranarayanan,
A.K.Das.
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ABSTRACT
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The low-molecular-weight protein tyrosine phosphatase (LMWPTPase) belongs to a
distinctive class of phosphotyrosine phosphatases widely distributed among
prokaryotes and eukaryotes. We report here the crystal structure of LMWPTPase of
microbial origin, the first of its kind from Mycobacterium tuberculosis. The
structure was determined to be two crystal forms at 1.9- and 2.5-A resolutions.
These structural forms are compared with those of the LMWPTPases of eukaryotes.
Though the overall structure resembles that of the eukaryotic LMWPTPases, there
are significant changes around the active site and the protein tyrosine
phosphatase (PTP) loop. The variable loop forming the wall of the crevice
leading to the active site is conformationally unchanged from that of mammalian
LMWPTPase; however, differences are observed in the residues involved,
suggesting that they have a role in influencing different substrate
specificities. The single amino acid substitution (Leu12Thr [underlined below])
in the consensus sequence of the PTP loop, CTGNICRS, has a major role in the
stabilization of the PTP loop, unlike what occurs in mammalian LMWPTPases. A
chloride ion and a glycerol molecule were modeled in the active site where the
chloride ion interacts in a manner similar to that of phosphate with the main
chain nitrogens of the PTP loop. This structural study, in addition to
identifying specific mycobacterial features, may also form the basis for
exploring the mechanism of the substrate specificities of bacterial LMWPTPases.
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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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K.Chandra,
D.Dutta,
A.Mitra,
A.K.Das,
and
A.Basak
(2011).
Design, synthesis and inhibition activity of a novel cyclic enediyne amino acid conjugates against MPtpA.
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Bioorg Med Chem, 19,
3274-3279.
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J.Blobel,
P.Bernadó,
H.Xu,
C.Jin,
and
M.Pons
(2009).
Weak oligomerization of low-molecular-weight protein tyrosine phosphatase is conserved from mammals to bacteria.
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FEBS J, 276,
4346-4357.
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K.A.Rawls,
P.T.Lang,
J.Takeuchi,
S.Imamura,
T.D.Baguley,
C.Grundner,
T.Alber,
and
J.A.Ellman
(2009).
Fragment-based discovery of selective inhibitors of the Mycobacterium tuberculosis protein tyrosine phosphatase PtpA.
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Bioorg Med Chem Lett, 19,
6851-6854.
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C.Madhurantakam,
V.R.Chavali,
and
A.K.Das
(2008).
Analyzing the catalytic mechanism of MPtpA: a low molecular weight protein tyrosine phosphatase from Mycobacterium tuberculosis through site-directed mutagenesis.
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Proteins, 71,
706-714.
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H.Bach,
K.G.Papavinasasundaram,
D.Wong,
Z.Hmama,
and
Y.Av-Gay
(2008).
Mycobacterium tuberculosis virulence is mediated by PtpA dephosphorylation of human vacuolar protein sorting 33B.
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Cell Host Microbe, 3,
316-322.
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M.R.Groves,
I.B.Müller,
X.Kreplin,
and
J.Müller-Dieckmann
(2007).
A method for the general identification of protein crystals in crystallization experiments using a noncovalent fluorescent dye.
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Acta Crystallogr D Biol Crystallogr, 63,
526-535.
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PDB codes:
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D.Tolkatchev,
R.Shaykhutdinov,
P.Xu,
J.Plamondon,
D.C.Watson,
N.M.Young,
and
F.Ni
(2006).
Three-dimensional structure and ligand interactions of the low molecular weight protein tyrosine phosphatase from Campylobacter jejuni.
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Protein Sci, 15,
2381-2394.
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PDB code:
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H.A.Watkins,
and
E.N.Baker
(2006).
Structural and functional analysis of Rv3214 from Mycobacterium tuberculosis, a protein with conflicting functional annotations, leads to its characterization as a phosphatase.
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J Bacteriol, 188,
3589-3599.
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PDB code:
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H.Xu,
B.Xia,
and
C.Jin
(2006).
Solution structure of a low-molecular-weight protein tyrosine phosphatase from Bacillus subtilis.
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J Bacteriol, 188,
1509-1517.
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PDB code:
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C.Grundner,
H.L.Ng,
and
T.Alber
(2005).
Mycobacterium tuberculosis protein tyrosine phosphatase PtpB structure reveals a diverged fold and a buried active site.
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Structure, 13,
1625-1634.
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PDB code:
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K.Saxena,
B.Elshorst,
H.Berk,
M.Betz,
S.Grimme,
T.Langer,
B.Pescatore,
U.Schieborr,
M.Vogtherr,
and
H.Schwalbe
(2005).
Backbone NMR assignment of the low-molecular-weight protein tyrosine phosphatase (MPtpA) from Mycobacterium tuberculosis.
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J Biomol NMR, 33,
136.
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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
