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PDBsum entry 1p03
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Hydrolase/hydrolase inhibitor
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PDB id
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1p03
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structural analysis of specificity: alpha-Lytic protease complexes with analogues of reaction intermediates.
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Authors
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R.Bone,
D.Frank,
C.A.Kettner,
D.A.Agard.
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Ref.
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Biochemistry, 1989,
28,
7600-7609.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
perfect match.
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Abstract
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To better understand the structural basis of enzyme specificity, the structures
of complexes formed between alpha-lytic protease, an extracellular serine
protease of Lysobacter enzymogenes, and five inhibitory peptide boronic acids
(R2-boroX, where R2 is methoxysuccinyl-Ala-Ala-Pro- and boroX is the
alpha-aminoboronic acid analogue of Ala, Val, Ile, Norleu, or Phe) have been
studied at high resolution by X-ray crystallography. The enzyme has primary
specificity for Ala in the P1 position of peptide substrates with catalytic
efficiency decreasing with increasing side-chain volume. Enzyme affinity for
inhibitors with boroVal, boroIle, and boroPhe residues is much higher than
expected on the basis of the catalytic efficiencies of homologous substrates.
Covalent tetrahedral adducts are formed between the active-site serine and the
boronic acid moieties of R2-boroAla, R2-boroVal R2-boroIle, and R2-boroNorleu.
Though R2-boroVal is a slowly bound inhibitor and R2-boroAla is rapidly bound
[Kettner, C. A., Bone, R., Agard, D. A., & Bachovchin, W. W. (1988)
Biochemistry 27, 7682-7688], there appear to be no structural differences that
could account for slow binding. The removal from solution of 20% more
hydrophobic surface on binding accounts for the improved affinity of alpha-lytic
protease for R2-boroVal relative to R2-boroAla. The high affinity of the enzyme
for R2-boroIle derives from the selective binding of the L-allo stereoisomer of
the boroIle residue, which can avoid bad steric interactions in the binding
pocket.(ABSTRACT TRUNCATED AT 250 WORDS)
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Secondary reference #1
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Title
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Structural plasticity broadens the specificity of an engineered protease.
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Authors
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R.Bone,
J.L.Silen,
D.A.Agard.
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Ref.
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Nature, 1989,
339,
191-195.
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above were
obtained from the PDBe's
server.
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Secondary reference #2
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Title
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Kinetic properties of the binding of alpha-Lytic protease to peptide boronic acids.
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Authors
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C.A.Kettner,
R.Bone,
D.A.Agard,
W.W.Bachovchin.
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Ref.
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Biochemistry, 1988,
27,
7682-7688.
[DOI no: ]
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PubMed id
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Secondary reference #3
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Title
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Serine protease mechanism: structure of an inhibitory complex of alpha-Lytic protease and a tightly bound peptide boronic acid.
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Authors
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R.Bone,
A.B.Shenvi,
C.A.Kettner,
D.A.Agard.
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Ref.
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Biochemistry, 1987,
26,
7609-7614.
[DOI no: ]
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PubMed id
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Secondary reference #4
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Title
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Refined structure of alpha-Lytic protease at 1.7 a resolution. Analysis of hydrogen bonding and solvent structure.
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Authors
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M.Fujinaga,
L.T.Delbaere,
G.D.Brayer,
M.N.James.
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Ref.
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J Mol Biol, 1985,
184,
479-502.
[DOI no: ]
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PubMed id
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Figure 8.
Figure 8. (a) The region around &-Pro95 that is in a reverse open turn conformation (Ramachandran & Mitra, 1976).
(Hydrogen bonds are shown by broken lines.) (b) The homologous region in SGPA is shown (continuous line and abeled
residues) superimposed on the equivalent residues of a-lytic rotease broken lines). The superposition was done using ll
the a-carbons in each molecule.
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Figure 14.
Figure 14. Hydrogen-onding involving the buried chrged residues Arg138 and Asp194. The boken lines show theFigure 14. Hydrogen-onding involving the buried chrged residues Arg138 and Asp194. The boken lines show the
ydrogen bonds. 02 is a tightly bonded internal water molecule. The interaction between the charged residues isydrogen bonds. 02 is a tightly bonded internal water molecule. The interaction between the charged residues is
mediated by Thr143.mediated by Thr143.
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The above figures are
reproduced from the cited reference
with permission from Elsevier
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Secondary reference #5
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Title
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Molecular structure of the alpha-Lytic protease from myxobacter 495 at 2.8 angstroms resolution.
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Authors
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G.D.Brayer,
L.T.Delbaere,
M.N.James.
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Ref.
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J Mol Biol, 1979,
131,
743-775.
[DOI no: ]
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PubMed id
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Figure 4.
FIG. 4. lot of the #I+% torsional angles for the atomic model of a-lytic proease at 2.8 A resolution.
The area enclosed within the solid lines of this plot is the fully allowed conformational region for
7 (Ca) of 110''; hhe broken line indicates the outer limit of acceptable van der Weals' contacts for
7 (Cm) of 115''. The following symbols are used for amino acid residue designation: (A) p-branched
amino acids; (0) glycine; I) proline; (+) others.
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Figure 6.
LEU
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The above figures are
reproduced from the cited reference
with permission from Elsevier
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