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PDBsum entry 1ft7
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* Residue conservation analysis
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Enzyme class:
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E.C.3.4.11.10
- bacterial leucyl aminopeptidase.
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Reaction:
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Release of an N-terminal amino acid, preferentially leucine, but not glutamic or aspartic acids.
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Cofactor:
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Zn(2+)
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Biochemistry
40:7035-7046
(2001)
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PubMed id:
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Inhibition of the aminopeptidase from Aeromonas proteolytica by L-leucinephosphonic acid. Spectroscopic and crystallographic characterization of the transition state of peptide hydrolysis.
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C.Stamper,
B.Bennett,
T.Edwards,
R.C.Holz,
D.Ringe,
G.Petsko.
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ABSTRACT
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The nature of the interaction of the transition-state analogue inhibitor
L-leucinephosphonic acid (LPA) with the leucine aminopeptidase from Aeromonas
proteolytica (AAP) was investigated. LPA was shown to be a competitive inhibitor
at pH 8.0 with a K(i) of 6.6 microM. Electronic absorption spectra, recorded at
pH 7.5 of [CoCo(AAP)], [CoZn(AAP)], and [ZnCo(AAP)] upon addition of LPA suggest
that LPA interacts with both metal ions in the dinuclear active site. EPR
studies on the Co(II)-substituted forms of AAP revealed that the environments of
the Co(II) ions in both [CoZn(AAP)] and [ZnCo(AAP)] become highly asymmetric and
constrained upon the addition of LPA and clearly indicate that LPA interacts
with both metal ions. The X-ray crystal structure of AAP complexed with LPA was
determined at 2.1 A resolution. The X-ray crystallographic data indicate that
LPA interacts with both metal centers in the dinuclear active site of AAP and a
single oxygen atom bridge is absent. Thus, LPA binds to the dinuclear active
site of AAP as an eta-1,2-mu-phosphonate with one ligand to the second metal ion
provided by the N-terminal amine. A structural comparison of the binding of
phosphonate-containing transition-state analogues to the mono- and bimetallic
peptidases provides insight into the requirement for the second metal ion in
bridged bimetallic peptidases. On the basis of the results obtained from the
spectroscopic and X-ray crystallographic data presented herein along with
previously reported mechanistic data for AAP, a new catalytic mechanism for the
hydrolysis reaction catalyzed by AAP is proposed.
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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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G.D.Tibhe,
V.Labastida-Galván,
and
M.Ordóñez
(2011).
Study of the fragmentation pathway of α-aminophosphonates by chemical ionization and fast atom bombardment mass spectrometry.
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Rapid Commun Mass Spectrom,
25,
951-959.
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M.A.Durá,
E.Rosenbaum,
A.Larabi,
F.Gabel,
F.M.Vellieux,
and
B.Franzetti
(2009).
The structural and biochemical characterizations of a novel TET peptidase complex from Pyrococcus horikoshii reveal an integrated peptide degradation system in hyperthermophilic Archaea.
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Mol Microbiol,
72,
26-40.
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PDB codes:
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M.Hartley,
and
B.Bennett
(2009).
Heterologous expression and purification of Vibrio proteolyticus (Aeromonas proteolytica) aminopeptidase: a rapid protocol.
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Protein Expr Purif,
66,
91.
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PDB code:
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M.Ordóñez,
H.Rojas-Cabrera,
and
C.Cativiela
(2009).
An Overview of Stereoselective Synthesis of α-Aminophosphonic Acids and Derivatives.
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Tetrahedron,
65,
17-49.
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G.Schoehn,
F.M.Vellieux,
M.Asunción Durá,
V.Receveur-Bréchot,
C.M.Fabry,
R.W.Ruigrok,
C.Ebel,
A.Roussel,
and
B.Franzetti
(2006).
An archaeal peptidase assembles into two different quaternary structures: A tetrahedron and a giant octahedron.
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J Biol Chem,
281,
36327-36337.
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PDB code:
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J.Arima,
Y.Uesugi,
M.Uraji,
S.Yatsushiro,
S.Tsuboi,
M.Iwabuchi,
and
T.Hatanaka
(2006).
Modulation of Streptomyces leucine aminopeptidase by calcium: identification and functional analysis of key residues in activation and stabilization by calcium.
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J Biol Chem,
281,
5885-5894.
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L.M.Berreau,
A.Saha,
and
A.M.Arif
(2006).
Thioester hydrolysis reactivity of zinc hydroxide complexes: investigating reactivity relevant to glyoxalase II enzymes.
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Dalton Trans,
(),
183-192.
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T.K.Sigdel,
R.Cilliers,
P.R.Gursahaney,
P.Thompson,
J.A.Easton,
and
M.W.Crowder
(2006).
Probing the adaptive response of Escherichia coli to extracellular Zn(II).
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Biometals,
19,
461-471.
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W.Desmarais,
D.L.Bienvenue,
K.P.Bzymek,
G.A.Petsko,
D.Ringe,
and
R.C.Holz
(2006).
The high-resolution structures of the neutral and the low pH crystals of aminopeptidase from Aeromonas proteolytica.
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J Biol Inorg Chem,
11,
398-408.
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PDB codes:
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D.Liu,
B.W.Lepore,
G.A.Petsko,
P.W.Thomas,
E.M.Stone,
W.Fast,
and
D.Ringe
(2005).
Three-dimensional structure of the quorum-quenching N-acyl homoserine lactone hydrolase from Bacillus thuringiensis.
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Proc Natl Acad Sci U S A,
102,
11882-11887.
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PDB code:
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S.Russo,
and
U.Baumann
(2004).
Crystal structure of a dodecameric tetrahedral-shaped aminopeptidase.
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J Biol Chem,
279,
51275-51281.
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PDB code:
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M.Elstner,
Q.Cui,
P.Munih,
E.Kaxiras,
T.Frauenheim,
and
M.Karplus
(2003).
Modeling zinc in biomolecules with the self consistent charge-density functional tight binding (SCC-DFTB) method: applications to structural and energetic analysis.
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J Comput Chem,
24,
565-581.
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B.Bennett,
W.E.Antholine,
V.M.D'souza,
G.Chen,
L.Ustinyuk,
and
R.C.Holz
(2002).
Structurally distinct active sites in the copper(II)-substituted aminopeptidases from Aeromonas proteolytica and Escherichia coli.
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J Am Chem Soc,
124,
13025-13034.
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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
