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PDBsum entry 2w1v
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Contents |
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* Residue conservation analysis
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Enzyme class:
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E.C.3.5.1.3
- omega-amidase.
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Reaction:
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a monoamide of a dicarboxylate + H2O = a dicarboxylate + NH4+
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monoamide of a dicarboxylate
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+
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H2O
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=
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dicarboxylate
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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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Biochemistry
47:13514-13523
(2008)
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PubMed id:
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Functional proteomic and structural insights into molecular recognition in the nitrilase family enzymes.
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K.T.Barglow,
K.S.Saikatendu,
M.H.Bracey,
R.Huey,
G.M.Morris,
A.J.Olson,
R.C.Stevens,
B.F.Cravatt.
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ABSTRACT
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Nitrilases are a large and diverse family of nonpeptidic C-N hydrolases. The
mammalian genome encodes eight nitrilase enzymes, several of which remain poorly
characterized. Prominent among these are nitrilase-1 (Nit1) and nitrilase-2
(Nit2), which, despite having been shown to exert effects on cell growth and
possibly serving as tumor suppressor genes, are without known substrates or
selective inhibitors. In previous studies, we identified several nitrilases,
including Nit1 and Nit2, as targets for dipeptide-chloroacetamide activity-based
proteomics probes. Here, we have used these probes, in combination with
high-resolution crystallography and molecular modeling, to systematically map
the active site of Nit2 and identify residues involved in molecular recognition.
We report the 1.4 A crystal structure of mouse Nit2 and use this structure to
identify residues that discriminate probe labeling between the Nit1 and Nit2
enzymes. Interestingly, some of these residues are conserved across all
vertebrate Nit2 enzymes and, conversely, not found in any vertebrate Nit1
enzymes, suggesting that they are key discriminators of molecular recognition
between these otherwise highly homologous enzymes. Our findings thus point to a
limited set of active site residues that establish distinct patterns of
molecular recognition among nitrilases and provide chemical probes to
selectively perturb the function of these enzymes in biological systems.
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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.Huebner,
J.C.Saldivar,
J.Sun,
H.Shibata,
and
T.Druck
(2011).
Hits, Fhits and Nits: beyond enzymatic function.
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Adv Enzyme Regul,
51,
208-217.
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O.Kaplan,
K.Bezouška,
O.Plíhal,
R.Ettrich,
N.Kulik,
O.Vaněk,
D.Kavan,
O.Benada,
A.Malandra,
O.Sveda,
A.B.Veselá,
A.Rinágelová,
K.Slámová,
M.Cantarella,
J.Felsberg,
J.Dušková,
J.Dohnálek,
M.Kotik,
V.Křen,
and
L.Martínková
(2011).
Heterologous expression, purification and characterization of nitrilase from Aspergillus niger K10.
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BMC Biotechnol,
11,
2.
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B.F.Krasnikov,
C.H.Chien,
R.Nostramo,
J.T.Pinto,
E.Nieves,
M.Callaway,
J.Sun,
K.Huebner,
and
A.J.Cooper
(2009).
Identification of the putative tumor suppressor Nit2 as omega-amidase, an enzyme metabolically linked to glutamine and asparagine transamination.
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Biochimie,
91,
1072-1080.
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B.F.Krasnikov,
R.Nostramo,
J.T.Pinto,
and
A.J.Cooper
(2009).
Assay and purification of omega-amidase/Nit2, a ubiquitously expressed putative tumor suppressor, that catalyzes the deamidation of the alpha-keto acid analogues of glutamine and asparagine.
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Anal Biochem,
391,
144-150.
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J.Sun,
H.Okumura,
M.Yearsley,
W.Frankel,
L.Y.Fong,
T.Druck,
and
K.Huebner
(2009).
Nit1 and Fhit tumor suppressor activities are additive.
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J Cell Biochem,
107,
1097-1106.
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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.
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Links
