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PDBsum entry 1im5
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* Residue conservation analysis
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Enzyme class:
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E.C.3.5.1.19
- nicotinamidase.
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Reaction:
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nicotinamide + H2O = nicotinate + NH4+
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nicotinamide
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+
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H2O
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=
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nicotinate
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+
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NH4(+)
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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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Biochemistry
40:14166-14172
(2001)
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PubMed id:
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Crystal structure and mechanism of catalysis of a pyrazinamidase from Pyrococcus horikoshii.
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X.Du,
W.Wang,
R.Kim,
H.Yakota,
H.Nguyen,
S.H.Kim.
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ABSTRACT
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Bacterial pyrazinamidase (PZAase)/nicotinamidase converts pyrazinamide (PZA) to
ammonia and pyrazinoic acid, which is active against Mycobacterium tuberculosis.
Loss of PZAase activity is the major mechanism of pyrazinamide-resistance by M.
tuberculosis. We have determined the crystal structure of the gene product of
Pyrococcus horikoshii 999 (PH999), a PZAase, and its complex with zinc ion by
X-ray crystallography. The overall fold of PH999 is similar to that of
N-carbamoylsarcosine amidohydrolase (CSHase) of Arthrobacter sp. and YcaC of
Escherichia coli, a protein with unknown physiological function. The active site
of PH999 was identified by structural features that are also present in the
active sites of CSHase and YcaC: a triad (D10, K94, and C133) and a cis-peptide
(between V128 and A129). Surprisingly, a metal ion-binding site was revealed in
the active site and subsequently confirmed by crystal structure of PH999 in
complex with Zn(2+). The roles of the triad, cis-peptide, and metal ion in the
catalysis are proposed. Because of extensive homology between PH999 and PZAase
of M. tuberculosis (37% sequence identity), the structure of PH999 provides a
structural basis for understanding PZA-resistance by M. tuberculosis harboring
PZAase mutations.
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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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S.Petrella,
N.Gelus-Ziental,
A.Maudry,
C.Laurans,
R.Boudjelloul,
and
W.Sougakoff
(2011).
Crystal Structure of the Pyrazinamidase of Mycobacterium tuberculosis: Insights into Natural and Acquired Resistance to Pyrazinamide.
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PLoS One,
6,
e15785.
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PDB code:
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H.B.Luo,
H.Zheng,
M.D.Zimmerman,
M.Chruszcz,
T.Skarina,
O.Egorova,
A.Savchenko,
A.M.Edwards,
and
W.Minor
(2010).
Crystal structure and molecular modeling study of N-carbamoylsarcosine amidase Ta0454 from Thermoplasma acidophilum.
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J Struct Biol,
169,
304-311.
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PDB code:
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J.Jonmalung,
T.Prammananan,
M.Leechawengwongs,
and
A.Chaiprasert
(2010).
Surveillance of pyrazinamide susceptibility among multidrug-resistant Mycobacterium tuberculosis isolates from Siriraj Hospital, Thailand.
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BMC Microbiol,
10,
223.
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K.M.McCulloch,
T.Mukherjee,
T.P.Begley,
and
S.E.Ealick
(2010).
Structure determination and characterization of the vitamin B6 degradative enzyme (E)-2-(acetamidomethylene)succinate hydrolase.
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Biochemistry,
49,
1226-1235.
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PDB code:
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M.Zimic,
P.Sheen,
M.Quiliano,
A.Gutierrez,
and
R.H.Gilman
(2010).
Peruvian and globally reported amino acid substitutions on the Mycobacterium tuberculosis pyrazinamidase suggest a conserved pattern of mutations associated to pyrazinamide resistance.
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Infect Genet Evol,
10,
346-349.
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P.Sheen,
P.Ferrer,
R.H.Gilman,
J.López-Llano,
P.Fuentes,
E.Valencia,
and
M.J.Zimic
(2009).
Effect of pyrazinamidase activity on pyrazinamide resistance in Mycobacterium tuberculosis.
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Tuberculosis (Edinb),
89,
109-113.
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T.L.Vrablik,
L.Huang,
S.E.Lange,
and
W.Hanna-Rose
(2009).
Nicotinamidase modulation of NAD+ biosynthesis and nicotinamide levels separately affect reproductive development and cell survival in C. elegans.
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Development,
136,
3637-3646.
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H.Zhang,
J.Y.Deng,
L.J.Bi,
Y.F.Zhou,
Z.P.Zhang,
C.G.Zhang,
Y.Zhang,
and
X.E.Zhang
(2008).
Characterization of Mycobacterium tuberculosis nicotinamidase/pyrazinamidase.
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FEBS J,
275,
753-762.
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J.I.Jiménez,
A.Canales,
J.Jiménez-Barbero,
K.Ginalski,
L.Rychlewski,
J.L.García,
and
E.Díaz
(2008).
Deciphering the genetic determinants for aerobic nicotinic acid degradation: the nic cluster from Pseudomonas putida KT2440.
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Proc Natl Acad Sci U S A,
105,
11329-11334.
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M.Babor,
S.Gerzon,
B.Raveh,
V.Sobolev,
and
M.Edelman
(2008).
Prediction of transition metal-binding sites from apo protein structures.
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Proteins,
70,
208-217.
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V.Balan,
G.S.Miller,
L.Kaplun,
K.Balan,
Z.Z.Chong,
F.Li,
A.Kaplun,
M.F.Vanberkum,
R.Arking,
D.C.Freeman,
K.Maiese,
and
G.Tzivion
(2008).
Life span extension and neuronal cell protection by Drosophila nicotinamidase.
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J Biol Chem,
283,
27810-27819.
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G.Hu,
A.B.Taylor,
L.McAlister-Henn,
and
P.J.Hart
(2007).
Crystal structure of the yeast nicotinamidase Pnc1p.
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Arch Biochem Biophys,
461,
66-75.
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PDB code:
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C.M.Gallo,
D.L.Smith,
and
J.S.Smith
(2004).
Nicotinamide clearance by Pnc1 directly regulates Sir2-mediated silencing and longevity.
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Mol Cell Biol,
24,
1301-1312.
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J.E.Purser,
M.B.Lawrenz,
M.J.Caimano,
J.K.Howell,
J.D.Radolf,
and
S.J.Norris
(2003).
A plasmid-encoded nicotinamidase (PncA) is essential for infectivity of Borrelia burgdorferi in a mammalian host.
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Mol Microbiol,
48,
753-764.
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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
code is
shown on the right.
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Links
