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* Residue conservation analysis
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Enzyme class:
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Chain A:
E.C.3.2.1.1
- Alpha-amylase.
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Reaction:
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Endohydrolysis of 1,4-alpha-glucosidic linkages in oligosaccharides and polysaccharides.
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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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2 terms
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Biological process
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metabolic process
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3 terms
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Biochemical function
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catalytic activity
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11 terms
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DOI no:
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Structure
4:1441-1452
(1996)
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PubMed id:
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Substrate mimicry in the active center of a mammalian alpha-amylase: structural analysis of an enzyme-inhibitor complex.
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C.Bompard-Gilles,
P.Rousseau,
P.Rougé,
F.Payan.
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ABSTRACT
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BACKGROUND: alpha-Amylases catalyze the hydrolysis of glycosidic linkages in
starch and other related polysaccharides. The alpha-amylase inhibitor (alpha-Al)
from the bean Phaseolus vulgaris belongs to a family of plant defence proteins
and is a potent inhibitor of mammalian alpha-amylases. The structure of pig
pancreatic alpha-amylase (PPA) in complex with both a carbohydrate inhibitor
(acarbose) and a proteinaceous inhibitor (Tendamistat) is known, but the
catalytic mechanism is poorly understood. RESULTS: The crystal structure of pig
pancreatic alpha-amylase complexed with alpha-Al was refined to 1.85 A
resolution. It reveals that in complex with PPA, the inhibitor has the typical
dimer structure common to legume lectins. Two hairpin loops extending out from
the jellyroll fold of a monomer interact directly with the active site region of
the enzyme molecule, with the inhibitor molecule filling the whole
substrate-docking region of the PPA. The inhibitor makes substrate-mimetic
interactions with binding subsites of the enzyme and targets catalytic residues
in the active site. Binding of inhibitor induces structural changes at the
active site of the enzyme. CONCLUSIONS: The present analysis reveals that there
are extensive interactions between the inhibitor and residues that are highly
conserved in the active site of alpha-amylases; alpha-Al1 inactivates PPA
through elaborate blockage of substrate-binding sites. It provides a basis to
design peptide analogue inhibitors. alpha-Amylase inhibition is of interest from
several points of view, for example the treatment of diabetes and for crop
protection.
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Selected figure(s)
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Figure 6.
Figure 6. Schematic representation of the network of
interactions within the catalytic center. The enzyme chloride
ion is shown in interaction with some of its ligands (Arg195,
Asn298 and H[2]0). The calcium ion of the enzyme structure
(liganded to Asn100 and His201) and the presumed calcium ion of
the inhibitor structure are involved in the interaction.
(Borders around inhibitor residues are thickened.)
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The above figure is
reprinted
by permission from Cell Press:
Structure
(1996,
4,
1441-1452)
copyright 1996.
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Figure was
selected
by an automated process.
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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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B.Nocek,
L.Bigelow,
J.Abdullah,
and
A.Joachimiak
(2008).
Structure of SO2946 orphan from Shewanella oneidensis shows "jelly-roll" fold with carbohydrate-binding module.
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J Struct Funct Genomics, 9,
1-6.
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PDB code:
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W.C.Obiro,
T.Zhang,
and
B.Jiang
(2008).
The nutraceutical role of the Phaseolus vulgaris alpha-amylase inhibitor.
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Br J Nutr, 100,
1.
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M.N.Dharmasena,
D.A.Jewell,
and
R.K.Taylor
(2007).
Development of peptide mimics of a protective epitope of Vibrio cholerae Ogawa O-antigen and investigation of the structural basis of peptide mimicry.
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J Biol Chem, 282,
33805-33816.
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Y.H.Kim,
C.P.Woloshuk,
E.H.Cho,
J.M.Bae,
Y.S.Song,
and
G.H.Huh
(2007).
Cloning and functional expression of the gene encoding an inhibitor against Aspergillus flavus alpha-amylase, a novel seed lectin from Lablab purpureus (Dolichos lablab).
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Plant Cell Rep, 26,
395-405.
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P.B.Pelegrini,
A.M.Murad,
M.F.Grossi-de-Sá,
L.V.Mello,
L.A.Romeiro,
E.F.Noronha,
R.A.Caldas,
and
O.L.Franco
(2006).
Structure and enzyme properties of Zabrotes subfasciatus alpha-amylase.
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Arch Insect Biochem Physiol, 61,
77-86.
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B.C.Bønsager,
P.K.Nielsen,
M.Abou Hachem,
K.Fukuda,
M.Praetorius-Ibba,
and
B.Svensson
(2005).
Mutational analysis of target enzyme recognition of the beta-trefoil fold barley alpha-amylase/subtilisin inhibitor.
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J Biol Chem, 280,
14855-14864.
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F.Rodier,
R.P.Bahadur,
P.Chakrabarti,
and
J.Janin
(2005).
Hydration of protein-protein interfaces.
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Proteins, 60,
36-45.
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L.Dolecková-Maresová,
M.Pavlík,
M.Horn,
and
M.Mares
(2005).
De novo design of alpha-amylase inhibitor: a small linear mimetic of macromolecular proteinaceous ligands.
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Chem Biol, 12,
1349-1357.
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N.Pohl
(2005).
Acyclic peptide inhibitors of amylases.
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Chem Biol, 12,
1257-1258.
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W.Hashimoto,
K.Momma,
Y.Maruyama,
M.Yamasaki,
B.Mikami,
and
K.Murata
(2005).
Structure and function of bacterial super-biosystem responsible for import and depolymerization of macromolecules.
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Biosci Biotechnol Biochem, 69,
673-692.
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A.H.Parret,
L.Wyns,
R.De Mot,
and
R.Loris
(2004).
Overexpression, purification and crystallization of bacteriocin LlpA from Pseudomonas sp. BW11M1.
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Acta Crystallogr D Biol Crystallogr, 60,
1922-1924.
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F.Payan,
P.Leone,
S.Porciero,
C.Furniss,
T.Tahir,
G.Williamson,
A.Durand,
P.Manzanares,
H.J.Gilbert,
N.Juge,
and
A.Roussel
(2004).
The dual nature of the wheat xylanase protein inhibitor XIP-I: structural basis for the inhibition of family 10 and family 11 xylanases.
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J Biol Chem, 279,
36029-36037.
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PDB codes:
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M.Yamasaki,
S.Moriwaki,
O.Miyake,
W.Hashimoto,
K.Murata,
and
B.Mikami
(2004).
Structure and function of a hypothetical Pseudomonas aeruginosa protein PA1167 classified into family PL-7: a novel alginate lyase with a beta-sandwich fold.
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J Biol Chem, 279,
31863-31872.
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PDB code:
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W.Hashimoto,
M.Yamasaki,
T.Itoh,
K.Momma,
B.Mikami,
and
K.Murata
(2004).
Super-channel in bacteria: structural and functional aspects of a novel biosystem for the import and depolymerization of macromolecules.
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J Biosci Bioeng, 98,
399-413.
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E.Ben-Zeev,
A.Berchanski,
A.Heifetz,
B.Shapira,
and
M.Eisenstein
(2003).
Prediction of the unknown: inspiring experience with the CAPRI experiment.
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Proteins, 52,
41-46.
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V.König,
L.Vértesy,
and
T.R.Schneider
(2003).
Structure of the alpha-amylase inhibitor tendamistat at 0.93 A.
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Acta Crystallogr D Biol Crystallogr, 59,
1737-1743.
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PDB code:
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A.Desmyter,
S.Spinelli,
F.Payan,
M.Lauwereys,
L.Wyns,
S.Muyldermans,
and
C.Cambillau
(2002).
Three camelid VHH domains in complex with porcine pancreatic alpha-amylase. Inhibition and versatility of binding topology.
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J Biol Chem, 277,
23645-23650.
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PDB codes:
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M.A.Johnson,
A.Rotondo,
and
B.M.Pinto
(2002).
NMR studies of the antibody-bound conformation of a carbohydrate-mimetic peptide.
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Biochemistry, 41,
2149-2157.
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O.L.Franco,
D.J.Rigden,
F.R.Melo,
and
M.F.Grossi-De-Sá
(2002).
Plant alpha-amylase inhibitors and their interaction with insect alpha-amylases.
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Eur J Biochem, 269,
397-412.
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P.Chakrabarti,
and
J.Janin
(2002).
Dissecting protein-protein recognition sites.
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Proteins, 47,
334-343.
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T.R.Schneider
(2002).
A genetic algorithm for the identification of conformationally invariant regions in protein molecules.
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Acta Crystallogr D Biol Crystallogr, 58,
195-208.
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Y.Kaneda,
R.F.Whittier,
H.Yamanaka,
E.Carredano,
M.Gotoh,
H.Sota,
Y.Hasegawa,
and
Y.Shinohara
(2002).
The high specificities of Phaseolus vulgaris erythro- and leukoagglutinating lectins for bisecting GlcNAc or beta 1-6-linked branch structures, respectively, are attributable to loop B.
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J Biol Chem, 277,
16928-16935.
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A.M.Fakhoury,
and
C.P.Woloshuk
(2001).
Inhibition of growth of Aspergillus flavus and fungal alpha-amylases by a lectin-like protein from Lablab purpureus.
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Mol Plant Microbe Interact, 14,
955-961.
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C.Kleanthous,
and
D.Walker
(2001).
Immunity proteins: enzyme inhibitors that avoid the active site.
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Trends Biochem Sci, 26,
624-631.
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H.J.Gabius
(2001).
Glycohistochemistry: the why and how of detection and localization of endogenous lectins.
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Anat Histol Embryol, 30,
3.
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D.Jain,
K.Kaur,
B.Sundaravadivel,
and
D.M.Salunke
(2000).
Structural and functional consequences of peptide-carbohydrate mimicry. Crystal structure of a carbohydrate-mimicking peptide bound to concanavalin A.
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J Biol Chem, 275,
16098-16102.
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PDB code:
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E.J.Van Damme,
C.H.Astoul,
A.Barre,
P.Rougé,
and
W.J.Peumans
(2000).
Cloning and characterization of a monocot mannose-binding lectin from Crocus vernus (family Iridaceae).
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Eur J Biochem, 267,
5067-5077.
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K.W.Rodenburg,
F.Vallée,
N.Juge,
N.Aghajari,
X.Guo,
R.Haser,
and
B.Svensson
(2000).
Specific inhibition of barley alpha-amylase 2 by barley alpha-amylase/subtilisin inhibitor depends on charge interactions and can be conferred to isozyme 1 by mutation.
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Eur J Biochem, 267,
1019-1029.
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E.H.Rydberg,
G.Sidhu,
H.C.Vo,
J.Hewitt,
H.C.Côte,
Y.Wang,
S.Numao,
R.T.MacGillivray,
C.M.Overall,
G.D.Brayer,
and
S.G.Withers
(1999).
Cloning, mutagenesis, and structural analysis of human pancreatic alpha-amylase expressed in Pichia pastoris.
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Protein Sci, 8,
635-643.
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PDB code:
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R.Koukiekolo,
V.Le Berre-Anton,
V.Desseaux,
Y.Moreau,
P.Rougé,
G.Marchis-Mouren,
and
M.Santimone
(1999).
Mechanism of porcine pancreatic alpha-amylase inhibition of amylose and maltopentaose hydrolysis by kidney bean (Phaseolus vulgaris) inhibitor and comparison with that by acarbose.
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Eur J Biochem, 265,
20-26.
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S.Darnis,
N.Juge,
X.J.Guo,
G.Marchis-Mouren,
A.Puigserver,
and
J.C.Chaix
(1999).
Molecular cloning and primary structure analysis of porcine pancreatic alpha-amylase.
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Biochim Biophys Acta, 1430,
281-289.
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V.Nahoum,
F.Farisei,
V.Le-Berre-Anton,
M.P.Egloff,
P.Rougé,
E.Poerio,
and
F.Payan
(1999).
A plant-seed inhibitor of two classes of alpha-amylases: X-ray analysis of Tenebrio molitor larvae alpha-amylase in complex with the bean Phaseolus vulgaris inhibitor.
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Acta Crystallogr D Biol Crystallogr, 55,
360-362.
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PDB code:
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L.Mourey,
J.D.Pédelacq,
C.Birck,
C.Fabre,
P.Rougé,
and
J.P.Samama
(1998).
Crystal structure of the arcelin-1 dimer from Phaseolus vulgaris at 1.9-A resolution.
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J Biol Chem, 273,
12914-12922.
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PDB code:
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M.J.Cho,
S.S.Cha,
J.H.Park,
H.J.Cha,
H.S.Lee,
K.H.Park,
and
B.H.Oh
(1998).
Preliminary X-ray crystallographic analysis of a novel maltogenic amylase from Bacillus stearothermophilus ET1.
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Acta Crystallogr D Biol Crystallogr, 54,
416-418.
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T.R.Transue,
E.De Genst,
M.A.Ghahroudi,
L.Wyns,
and
S.Muyldermans
(1998).
Camel single-domain antibody inhibits enzyme by mimicking carbohydrate substrate.
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Proteins, 32,
515-522.
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L.Mourey,
J.D.Pédelacq,
C.Fabre,
H.Causse,
P.Rougé,
and
J.P.Samama
(1997).
Small-angle X-ray scattering and crystallographic studies of arcelin-1: an insecticidal lectin-like glycoprotein from Phaseolus vulgaris L.
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Proteins, 29,
433-442.
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M.Qian,
S.Spinelli,
H.Driguez,
and
F.Payan
(1997).
Structure of a pancreatic alpha-amylase bound to a substrate analogue at 2.03 A resolution.
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Protein Sci, 6,
2285-2296.
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PDB code:
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V.Le Berre-Anton,
C.Bompard-Gilles,
F.Payan,
and
P.Rougé
(1997).
Characterization and functional properties of the alpha-amylase inhibitor (alpha-AI) from kidney bean (Phaseolus vulgaris) seeds.
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Biochim Biophys Acta, 1343,
31-40.
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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
