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PDBsum entry 1aap
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Proteinase inhibitor (trypsin)
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PDB id
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1aap
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Contents |
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* Residue conservation analysis
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DOI no:
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Biochemistry
29:10018-10022
(1990)
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PubMed id:
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X-ray crystal structure of the protease inhibitor domain of Alzheimer's amyloid beta-protein precursor.
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T.R.Hynes,
M.Randal,
L.A.Kennedy,
C.Eigenbrot,
A.A.Kossiakoff.
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ABSTRACT
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Alzheimer's amyloid beta-protein precursor contains a Kunitz protease inhibitor
domain (APPI) potentially involved in proteolytic events leading to cerebral
amyloid deposition. To facilitate the identification of the physiological target
of the inhibitor, the crystal structure of APPI has been determined and refined
to 1.5-A resolution. Sequences in the inhibitor-protease interface of the
correct protease target will reflect the molecular details of the APPI
structure. While the overall tertiary fold of APPI is very similar to that of
the Kunitz inhibitor BPTI, a significant rearrangement occurs in the backbone
conformation of one of the two protease binding loops. A number of Kunitz
inhibitors have similar loop sequences, indicating the structural alteration is
conserved and potentially an important determinant of inhibitor specificity. In
a separate region of the protease binding loops, APPI side chains Met-17 and
Phe-34 create an exposed hydrophobic surface in place of Arg-17 and Val-34 in
BPTI. The restriction this change places on protease target sequences is seen
when the structure of APPI is superimposed on BPTI complexed to serine
proteases, where the hydrophobic surface of APPI faces a complementary group of
nonpolar side chains on kallikrein A versus polar side chains on trypsin.
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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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J.E.Swedberg,
S.J.de Veer,
and
J.M.Harris
(2010).
Natural and engineered kallikrein inhibitors: an emerging pharmacopoeia.
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Biol Chem,
391,
357-374.
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A.J.Beel,
C.K.Mobley,
H.J.Kim,
F.Tian,
A.Hadziselimovic,
B.Jap,
J.H.Prestegard,
and
C.R.Sanders
(2008).
Structural studies of the transmembrane C-terminal domain of the amyloid precursor protein (APP): does APP function as a cholesterol sensor?
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Biochemistry,
47,
9428-9446.
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D.Kaden,
L.M.Munter,
M.Joshi,
C.Treiber,
C.Weise,
T.Bethge,
P.Voigt,
M.Schaefer,
M.Beyermann,
B.Reif,
and
G.Multhaup
(2008).
Homophilic interactions of the amyloid precursor protein (APP) ectodomain are regulated by the loop region and affect beta-secretase cleavage of APP.
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J Biol Chem,
283,
7271-7279.
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S.Macedo-Ribeiro,
C.Almeida,
B.M.Calisto,
T.Friedrich,
R.Mentele,
J.Stürzebecher,
P.Fuentes-Prior,
and
P.J.Pereira
(2008).
Isolation, cloning and structural characterisation of boophilin, a multifunctional Kunitz-type proteinase inhibitor from the cattle tick.
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PLoS ONE,
3,
e1624.
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PDB code:
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M.Gralle,
and
S.T.Ferreira
(2007).
Structure and functions of the human amyloid precursor protein: the whole is more than the sum of its parts.
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Prog Neurobiol,
82,
11-32.
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A.Chakrabarty,
J.A.MacLean,
A.L.Hughes,
R.M.Roberts,
and
J.A.Green
(2006).
Rapid evolution of the trophoblast kunitz domain proteins (TKDPs)-a multigene family in ruminant ungulates.
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J Mol Evol,
63,
274-282.
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C.L.Masters,
R.Cappai,
K.J.Barnham,
and
V.L.Villemagne
(2006).
Molecular mechanisms for Alzheimer's disease: implications for neuroimaging and therapeutics.
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J Neurochem,
97,
1700-1725.
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D.Navaneetham,
L.Jin,
P.Pandey,
J.E.Strickler,
R.E.Babine,
S.S.Abdel-Meguid,
and
P.N.Walsh
(2005).
Structural and mutational analyses of the molecular interactions between the catalytic domain of factor XIa and the Kunitz protease inhibitor domain of protease nexin 2.
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J Biol Chem,
280,
36165-36175.
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PDB code:
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S.Herrero,
E.Combes,
M.M.Van Oers,
J.M.Vlak,
R.A.de Maagd,
and
J.Beekwilder
(2005).
Identification and recombinant expression of a novel chymotrypsin from Spodoptera exigua.
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Insect Biochem Mol Biol,
35,
1073-1082.
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A.E.Schmidt,
T.Ogawa,
D.Gailani,
and
S.P.Bajaj
(2004).
Structural role of Gly(193) in serine proteases: investigations of a G555E (GLY193 in chymotrypsin) mutant of blood coagulation factor XI.
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J Biol Chem,
279,
29485-29492.
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C.Keil,
R.Huber,
W.Bode,
and
M.E.Than
(2004).
Cloning, expression, crystallization and initial crystallographic analysis of the C-terminal domain of the amyloid precursor protein APP.
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Acta Crystallogr D Biol Crystallogr,
60,
1614-1617.
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M.G.Botelho,
M.Gralle,
C.L.Oliveira,
I.Torriani,
and
S.T.Ferreira
(2003).
Folding and stability of the extracellular domain of the human amyloid precursor protein.
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J Biol Chem,
278,
34259-34267.
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M.Gralle,
M.M.Botelho,
C.L.de Oliveira,
I.Torriani,
and
S.T.Ferreira
(2002).
Solution studies and structural model of the extracellular domain of the human amyloid precursor protein.
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Biophys J,
83,
3513-3524.
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I.Favre,
G.W.Moss,
D.P.Goldenberg,
J.Otlewski,
and
E.Moczydlowski
(2000).
Structure-activity relationships for the interaction of bovine pancreatic trypsin inhibitor with an intracellular site on a large conductance Ca(2+)-activated K(+) channel.
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Biochemistry,
39,
2001-2012.
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K.O.Badellino,
and
P.N.Walsh
(2000).
Protease nexin II interactions with coagulation factor XIa are contained within the Kunitz protease inhibitor domain of protease nexin II and the factor XIa catalytic domain.
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Biochemistry,
39,
4769-4777.
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B.Gilquin,
A.Lecoq,
F.Desné,
M.Guenneugues,
S.Zinn-Justin,
and
A.Ménez
(1999).
Conformational and functional variability supported by the BPTI fold: solution structure of the Ca2+ channel blocker calcicludine.
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Proteins,
34,
520-532.
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PDB code:
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R.D.Moir,
T.Lynch,
A.I.Bush,
S.Whyte,
A.Henry,
S.Portbury,
G.Multhaup,
D.H.Small,
R.E.Tanzi,
K.Beyreuther,
and
C.L.Masters
(1998).
Relative increase in Alzheimer's disease of soluble forms of cerebral Abeta amyloid protein precursor containing the Kunitz protease inhibitory domain.
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J Biol Chem,
273,
5013-5019.
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S.H.Wong,
T.Zhang,
Y.Xu,
V.N.Subramaniam,
G.Griffiths,
and
W.Hong
(1998).
Endobrevin, a novel synaptobrevin/VAMP-like protein preferentially associated with the early endosome.
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Mol Biol Cell,
9,
1549-1563.
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S.H.Wong,
Y.Xu,
T.Zhang,
and
W.Hong
(1998).
Syntaxin 7, a novel syntaxin member associated with the early endosomal compartment.
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J Biol Chem,
273,
375-380.
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A.J.Scheidig,
T.R.Hynes,
L.A.Pelletier,
J.A.Wells,
and
A.A.Kossiakoff
(1997).
Crystal structures of bovine chymotrypsin and trypsin complexed to the inhibitor domain of Alzheimer's amyloid beta-protein precursor (APPI) and basic pancreatic trypsin inhibitor (BPTI): engineering of inhibitors with altered specificities.
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Protein Sci,
6,
1806-1824.
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PDB codes:
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C.Capasso,
M.Rizzi,
E.Menegatti,
P.Ascenzi,
and
M.Bolognesi
(1997).
Crystal structure of the bovine alpha-chymotrypsin:Kunitz inhibitor complex. An example of multiple protein:protein recognition sites.
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J Mol Recognit,
10,
26-35.
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PDB code:
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J.Y.Duffy,
M.L.Stallings-Mann,
W.E.Trout,
and
R.M.Roberts
(1997).
Expression of a plasmin/trypsin Kunitz inhibitor by pig trophoblast.
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Mol Reprod Dev,
46,
443-449.
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M.D.Sorensen,
S.Bjorn,
K.Norris,
O.Olsen,
L.Petersen,
T.L.James,
and
J.J.Led
(1997).
Solution structure and backbone dynamics of the human alpha3-chain type VI collagen C-terminal Kunitz domain,.
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Biochemistry,
36,
10439-10450.
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PDB code:
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A.C.Ley,
W.Markland,
and
R.C.Ladner
(1996).
Obtaining a family of high-affinity, high-specificity protein inhibitors of plasmin and plasma kallikrein.
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Mol Divers,
2,
119-124.
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E.Kohfeldt,
W.Göhring,
U.Mayer,
M.Zweckstetter,
T.A.Holak,
M.L.Chu,
and
R.Timpl
(1996).
Conversion of the Kunitz-type module of collagen VI into a highly active trypsin inhibitor by site-directed mutagenesis.
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Eur J Biochem,
238,
333-340.
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L.C.Petersen,
S.E.Bjørn,
O.H.Olsen,
O.Nordfang,
F.Norris,
and
K.Norris
(1996).
Inhibitory properties of separate recombinant Kunitz-type-protease-inhibitor domains from tissue-factor-pathway inhibitor.
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Eur J Biochem,
235,
310-316.
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M.Zweckstetter,
M.Czisch,
U.Mayer,
M.L.Chu,
W.Zinth,
R.Timpl,
and
T.A.Holak
(1996).
Structure and multiple conformations of the kunitz-type domain from human type VI collagen alpha3(VI) chain in solution.
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Structure,
4,
195-209.
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W.Markland,
A.C.Ley,
S.W.Lee,
and
R.C.Ladner
(1996).
Iterative optimization of high-affinity proteases inhibitors using phage display. 1. Plasmin.
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Biochemistry,
35,
8045-8057.
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M.S.Dennis,
A.Herzka,
and
R.A.Lazarus
(1995).
Potent and selective Kunitz domain inhibitors of plasma kallikrein designed by phage display.
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J Biol Chem,
270,
25411-25417.
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M.S.Lim-Wilby,
K.Hallenga,
M.de Maeyer,
I.Lasters,
G.P.Vlasuk,
and
T.K.Brunck
(1995).
NMR structure determination of tick anticoagulant peptide (TAP).
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Protein Sci,
4,
178-186.
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PDB code:
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P.D.Kwong,
N.Q.McDonald,
P.B.Sigler,
and
W.A.Hendrickson
(1995).
Structure of beta 2-bungarotoxin: potassium channel binding by Kunitz modules and targeted phospholipase action.
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Structure,
3,
1109-1119.
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PDB code:
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R.C.Ladner
(1995).
Constrained peptides as binding entities.
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Trends Biotechnol,
13,
426-430.
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H.Schweitz,
C.Heurteaux,
P.Bois,
D.Moinier,
G.Romey,
and
M.Lazdunski
(1994).
Calcicludine, a venom peptide of the Kunitz-type protease inhibitor family, is a potent blocker of high-threshold Ca2+ channels with a high affinity for L-type channels in cerebellar granule neurons.
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Proc Natl Acad Sci U S A,
91,
878-882.
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K.Sorimachi,
and
D.J.Craik
(1994).
Structure determination of extracellular fragments of amyloid proteins involved in Alzheimer's disease and Dutch-type hereditary cerebral haemorrhage with amyloidosis.
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Eur J Biochem,
219,
237-251.
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U.Mayer,
E.Pöschl,
R.Nischt,
U.Specks,
T.C.Pan,
M.L.Chu,
and
R.Timpl
(1994).
Recombinant expression and properties of the Kunitz-type protease-inhibitor module from human type VI collagen alpha 3(VI) chain.
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Eur J Biochem,
225,
573-580.
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K.S.Kim,
F.Tao,
J.Fuchs,
A.T.Danishefsky,
D.Housset,
A.Wlodawer,
and
C.Woodward
(1993).
Crevice-forming mutants of bovine pancreatic trypsin inhibitor: stability changes and new hydrophobic surface.
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Protein Sci,
2,
588-596.
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T.E.Creighton,
and
J.Kemmink
(1993).
NOGGIN is unlikely to be homologous to the Kunitz protease-inhibitor family.
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Trends Biochem Sci,
18,
424-426.
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W.Antuch,
K.D.Berndt,
M.A.Chávez,
J.Delfín,
and
K.Wüthrich
(1993).
The NMR solution structure of a Kunitz-type proteinase inhibitor from the sea anemone Stichodactyla helianthus.
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Eur J Biochem,
212,
675-684.
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PDB code:
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M.Billeter
(1992).
Comparison of protein structures determined by NMR in solution and by X-ray diffraction in single crystals.
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Q Rev Biophys,
25,
325-377.
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M.D.Walkinshaw
(1992).
Protein targets for structure-based drug design.
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Med Res Rev,
12,
317-372.
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W.Bode,
and
R.Huber
(1992).
Natural protein proteinase inhibitors and their interaction with proteinases.
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Eur J Biochem,
204,
433-451.
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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
