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PDBsum entry 1zdp
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* Residue conservation analysis
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Enzyme class:
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E.C.3.4.24.27
- thermolysin.
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Reaction:
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Preferential cleavage: Xaa-|-Leu > Xaa-|-Phe.
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Cofactor:
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Ca(2+); Zn(2+)
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DOI no:
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Biochemistry
28:1493-1497
(1989)
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PubMed id:
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Thiorphan and retro-thiorphan display equivalent interactions when bound to crystalline thermolysin.
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S.L.Roderick,
M.C.Fournie-Zaluski,
B.P.Roques,
B.W.Matthews.
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ABSTRACT
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The three-dimensional structures of (S)-thiorphan and (R)-retro-thiorphan bound
to thermolysin have been determined crystallographically and refined to
residuals of 0.183 and 0.187 at 1.7-A resolution. Thiorphan
[N-[(S)-2-(mercaptomethyl)-1-oxo-3-phenylpropyl]glycine]
[HSCH2CH(CH2C6H5)CONHC-H2COOH] and retro-thiorphan
[[[(R)-1-(mercaptomethyl)-2-phenylethyl] amino]-3-oxopropanoic acid]
[HSCH2CH(CH2C6H5)NHCOCH2COOH] are isomeric thiol-containing inhibitors of
endopeptidase EC 24-11 (also called "enkephalinase"). The mode of binding of
thiorphan to thermolysin is similar to that of
(2-benzyl-3-mercaptopropanoyl)-L-alanylglycinamide [Monzingo, A.F., &
Matthews, B.W. (1982) Biochemistry 21, 3390-3394] with the inhibitor sulfur atom
coordinated to the active site zinc and the peptide portion forming
substrate-like interactions with the enzyme. The isomeric inhibitor
retro-thiorphan, which differs from thiorphan by the inversion of an amide bond,
utilizes very similar interactions with enzyme. Despite the inversion of the
-CO-NH- linkage the carbonyl oxygen and amide nitrogen display very similar
hydrogen bonding, as anticipated by B.P. Roques et al. [(1983) Proc. Natl. Acad.
Sci. U.S.A. 80, 3178-3182]. These results explain why thermolysin and possibly
other zinc endopeptidases such as endopeptidase EC 24-11 fail to discriminate
between these retro-inverso inhibitors.
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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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R.Wu,
P.Hu,
S.Wang,
Z.Cao,
and
Y.Zhang
(2009).
Flexibility of Catalytic Zinc Coordination in Thermolysin and HDAC8: A Born-Oppenheimer ab initio QM/MM Molecular Dynamics Study.
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J Chem Theory Comput,
6,
337.
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B.M.McArdle,
and
R.J.Quinn
(2007).
Identification of protein fold topology shared between different folds inhibited by natural products.
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Chembiochem,
8,
788-798.
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N.H.Gokhale,
S.Bradford,
and
J.A.Cowan
(2007).
Stimulation and oxidative catalytic inactivation of thermolysin by copper.Cys-Gly-His-Lys.
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J Biol Inorg Chem,
12,
981-987.
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M.Chorev,
and
M.Goodman
(2005).
The partial retro-inverso modification: a road traveled together.
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Biopolymers,
80,
67-84.
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C.Marie-Claire,
G.Tiraboschi,
E.Ruffet,
N.Inguimbert,
M.C.Fournie-Zaluski,
and
B.P.Roques
(2000).
Exploration of the S(')(1) subsite of neprilysin: a joined molecular modeling and site-directed mutagenesis study.
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Proteins,
39,
365-371.
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H.Kubinyi
(1998).
[Molecular similarity. 1. Chemical structure and biological action]
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Pharm Unserer Zeit,
27,
92.
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A.Beaumont,
M.J.O'Donohue,
N.Paredes,
N.Rousselet,
M.Assicot,
C.Bohuon,
M.C.Fournié-Zaluski,
and
B.P.Roques
(1995).
The role of histidine 231 in thermolysin-like enzymes. A site-directed mutagenesis study.
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J Biol Chem,
270,
16803-16808.
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C.McMartin,
and
R.S.Bohacek
(1995).
Flexible matching of test ligands to a 3D pharmacophore using a molecular superposition force field: comparison of predicted and experimental conformations of inhibitors of three enzymes.
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J Comput Aided Mol Des,
9,
237-250.
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R.S.Bohacek,
and
C.McMartin
(1995).
Exploring the universe of molecules for new drugs.
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Nat Med,
1,
177-178.
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H.J.Böhm
(1994).
The development of a simple empirical scoring function to estimate the binding constant for a protein-ligand complex of known three-dimensional structure.
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J Comput Aided Mol Des,
8,
243-256.
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H.Le Moual,
N.Dion,
B.P.Roques,
P.Crine,
and
G.Boileau
(1994).
Asp650 is crucial for catalytic activity of neutral endopeptidase 24-11.
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Eur J Biochem,
221,
475-480.
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M.C.Fournié-Zaluski,
W.Gonzalez,
S.Turcaud,
I.Pham,
B.P.Roques,
and
J.B.Michel
(1994).
Dual inhibition of angiotensin-converting enzyme and neutral endopeptidase by the orally active inhibitor mixanpril: a potential therapeutic approach in hypertension.
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Proc Natl Acad Sci U S A,
91,
4072-4076.
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B.P.Roques
(1992).
Peptidomimetics as receptors agonists or peptidase inhibitors: a structural approach in the field of enkephalins, ANP and CCK.
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Biopolymers,
32,
407-410.
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W.Stark,
R.A.Pauptit,
K.S.Wilson,
and
J.N.Jansonius
(1992).
The structure of neutral protease from Bacillus cereus at 0.2-nm resolution.
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Eur J Biochem,
207,
781-791.
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PDB code:
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B.P.Roques,
and
A.Beaumont
(1990).
Neutral endopeptidase-24.11 inhibitors: from analgesics to antihypertensives?
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Trends Pharmacol Sci,
11,
245-249.
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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
