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* Residue conservation analysis
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Enzyme class:
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Chains B, C, F, G:
E.C.3.4.21.1
- chymotrypsin.
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Reaction:
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Preferential cleavage: Tyr-|-Xaa, Trp-|-Xaa, Phe-|-Xaa, Leu-|-Xaa.
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J Biol Chem
262:7737-7743
(1987)
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PubMed id:
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Structure of a tetrahedral transition state complex of alpha-chymotrypsin dimer at 1.8-A resolution.
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A.Tulinsky,
R.A.Blevins.
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ABSTRACT
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A 1.8-A resolution x-ray crystallographic restrained least squares refinement
has been carried out on the phenylethane boronic acid (PEBA) complex of
alpha-chymotrypsin dimer (alpha-CHT), and it has been compared to the 1.67-A
resolution structure of the native enzyme. PEBA has a high binding affinity for
alpha-CHT, and the boronate forms a tetrahedral complex with Ser-195 OG of one
molecule of the dimer; the boronate in the other molecule is severely disordered
and does not form a tetrahedral complex. The former could be a model of the
transition state of catalysis. The complex of PEBA X alpha-CHT displays
significant nonequivalence in conformation of side chains between the
independent molecules comparable to the native enzyme, but, like the latter,
shows a high degree of fidelity in the folding of the main chain. The
orientation of the phenyl ring, CA and CB of PEBA, in the specificity sites of
the two molecules is similar, suggesting that recognition is fairly insensitive
to small departures from local symmetry; the same does not apply to the boronate
functionalities suggesting that greater precision is required for catalysis. The
folding of the molecule remains the same upon PEBA binding, but some of the side
chains respond nonequivalently. The latter is a consequence of the inherent
nonequivalence of the native dimer and the asymmetrical nature of the PEBA
binding.
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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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A.Moulin,
J.H.Bell,
R.F.Pratt,
and
D.Ringe
(2007).
Inhibition of chymotrypsin by a complex of ortho-vanadate and benzohydroxamic acid: structure of the inert complex and its mechanistic interpretation.
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Biochemistry,
46,
5982-5990.
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PDB code:
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G.Bruylants,
C.Redfield,
and
K.Bartik
(2007).
Developments in the characterisation of the catalytic triad of alpha-chymotrypsin: Effect of the protonation state of Asp102 on the 1H NMR signals of His57.
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Chembiochem,
8,
51-54.
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G.Bruylants,
R.Wintjens,
Y.Looze,
C.Redfield,
and
K.Bartik
(2007).
Protonation linked equilibria and apparent affinity constants: the thermodynamic profile of the alpha-chymotrypsin-proflavin interaction.
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Eur Biophys J,
37,
11-18.
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A.G.Cheetham,
M.G.Hutchings,
T.D.Claridge,
and
H.L.Anderson
(2006).
Enzymatic synthesis and photoswitchable enzymatic cleavage of a peptide-linked rotaxane.
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Angew Chem Int Ed Engl,
45,
1596-1599.
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N.Singh,
T.Jabeen,
S.Sharma,
I.Roy,
M.N.Gupta,
S.Bilgrami,
R.K.Somvanshi,
S.Dey,
M.Perbandt,
C.Betzel,
A.Srinivasan,
and
T.P.Singh
(2005).
Detection of native peptides as potent inhibitors of enzymes. Crystal structure of the complex formed between treated bovine alpha-chymotrypsin and an autocatalytically produced fragment, IIe-Val-Asn-Gly-Glu-Glu-Ala-Val-Pro-Gly-Ser-Trp-Pro-Trp, at 2.2 angstroms resolution.
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FEBS J,
272,
562-572.
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PDB code:
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P.K.Das,
J.M.Caaveiro,
S.Luque,
and
A.M.Klibanov
(2002).
Asymmetric sulfoxidations mediated by alpha-chymotrypsin.
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Biotechnol Bioeng,
78,
104-109.
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V.Z.Pletnev,
T.S.Zamolodchikova,
W.A.Pangborn,
and
W.L.Duax
(2000).
Crystal structure of bovine duodenase, a serine protease, with dual trypsin and chymotrypsin-like specificities.
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Proteins,
41,
8.
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PDB code:
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E.Szabó,
Z.Böcskei,
G.Náray-Szabó,
and
L.Gráf
(1999).
The three-dimensional structure of Asp189Ser trypsin provides evidence for an inherent structural plasticity of the protease.
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Eur J Biochem,
263,
20-26.
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PDB code:
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T.K.Harris,
and
A.S.Mildvan
(1999).
High-precision measurement of hydrogen bond lengths in proteins by nuclear magnetic resonance methods.
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Proteins,
35,
275-282.
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B.Koksch,
N.Sewald,
H.J.Hofmann,
K.Burger,
and
H.D.Jakubke
(1997).
Proteolytically stable peptides by incorporation of alpha-Tfm amino acids.
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J Pept Sci,
3,
157-167.
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V.Martichonok,
and
J.B.Jones
(1997).
Cysteine proteases such as papain are not inhibited by substrate analogue peptidyl boronic acids.
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Bioorg Med Chem,
5,
679-684.
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E.S.Stavridi,
K.O'Malley,
C.M.Lukacs,
W.T.Moore,
J.D.Lambris,
D.W.Christianson,
H.Rubin,
and
B.S.Cooperman
(1996).
Structural change in alpha-chymotrypsin induced by complexation with alpha 1-antichymotrypsin as seen by enhanced sensitivity to proteolysis.
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Biochemistry,
35,
10608-10615.
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R.Krishnan,
A.Tulinsky,
G.P.Vlasuk,
D.Pearson,
P.Vallar,
P.Bergum,
T.K.Brunck,
and
W.C.Ripka
(1996).
Synthesis, structure, and structure-activity relationships of divalent thrombin inhibitors containing an alpha-keto-amide transition-state mimetic.
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Protein Sci,
5,
422-433.
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PDB code:
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F.Björkling,
A.Dahl,
S.Patkar,
and
M.Zundel
(1994).
Inhibition of lipases by phosphonates.
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Bioorg Med Chem,
2,
697-705.
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P.D.Edwards,
and
P.R.Bernstein
(1994).
Synthetic inhibitors of elastase.
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Med Res Rev,
14,
127-194.
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W.G.Woods
(1994).
An introduction to boron: history, sources, uses, and chemistry.
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Environ Health Perspect,
102,
5.
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F.Adebodun,
and
F.Jordan
(1989).
Multinuclear magnetic resonance studies on serine protease transition state analogues.
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J Cell Biochem,
40,
249-260.
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S.Farr-Jones,
S.O.Smith,
C.A.Kettner,
R.G.Griffin,
and
W.W.Bachovchin
(1989).
Crystal versus solution structure of enzymes: NMR spectroscopy of a peptide boronic acid-serine protease complex in the crystalline state.
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Proc Natl Acad Sci U S A,
86,
6922-6924.
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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
