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PDBsum entry 1vwj
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Complex (biotin-binding protein/peptide)
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PDB id
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1vwj
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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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In crystals of complexes of streptavidin with peptide ligands containing the hpq sequence the pka of the peptide histidine is less than 3.0.
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Authors
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B.A.Katz,
R.T.Cass.
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Ref.
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J Biol Chem, 1997,
272,
13220-13228.
[DOI no: ]
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PubMed id
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Abstract
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The pH dependences of the affinities for streptavidin of linear and cyclic
peptide ligands containing the HPQ sequence discovered by phage display were
determined by plasmon resonance measurements. At pH values ranging from 3.0 to
9.0, the Kd values for Ac-AEFSHPQNTIEGRK-NH2, cyclo-Ac-AE[CHPQGPPC]IEGRK-NH2,
and cyclo-Ac-AE[CHPQFC]IEGRK-NH2, were determined by competition, and those for
cyclo-[5-S-valeramide-HPQGPPC]K-NH2 were determined directly by equilibrium
affinity measurements. The Kd values of the ligands increase by an average
factor of 3.0 +/- 0.8 per decrease in pH unit between pH approximately 4.5 and
pH approximately 6.3. Below pH approximately 4.5 there is a smaller increase in
Kd values, and above pH approximately 6.3 the Kd values become relatively
pH-independent. We determined the crystal structures of complexes of
streptavidin with cyclo-[5-S-valeramide-HPQGPPC]K-NH2 at pH 1.5, 2.5, 3.0, and
3.5, with cyclo-Ac-[CHPQFC]-NH2 at pH 2.0, 3.0, 3.6, 4.2, 4.8, and 11.8, with
cyclo-Ac-[CHPQGPPC]-NH2 at pH 2.5, 2.9, and 3.7, and with FSHPQNT at pH 4.0 and
compared the structures with one another and with those previously determined at
other pH values. At pH values from 3.0 to 11.8, the electron density for the
peptide His side chain is strong, flat, and well defined. A hydrogen bond
between the Ndelta1 atom of the His and the peptide Gln amide group indicates
the His of the bound peptide in the crystals is uncharged at pH >/= 3.0. By
determining selected structures in two different space groups, I222 with two
crystallographically inequivalent ligand sites and I4122 with one site, we show
that below pH approximately 3.0, the pKa of the bound peptide His in the
crystals is influenced by crystal packing interactions. The presence of the
Ndelta1His-NGln hydrogen bond along with pH dependences of the peptide
affinities suggest that deprotonation of the peptide His is required for high
affinity binding of HPQ-containing peptides to streptavidin both in the crystals
and in solution.
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Figure 3.
Fig. 3. A, low energy hydrogen bonding network for Trp79,
Thr90, a bound water, and the peptide Gln. B, alternate, higher
energy, hydrogen bonding scheme for these groups.
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Figure 4.
Fig. 4. Hydrogen bonding network in streptavidin-FSHPQNT.
Protein residues are white, peptide ligand is yellow-orange,
and^ bound waters are light blue.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(1997,
272,
13220-13228)
copyright 1997.
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Secondary reference #1
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Title
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Structure-Based design tools: structural and thermodynamic comparison with biotin of a small molecule that binds streptavidin with micromolar affinity
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Authors
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B.A.Katz,
B.Liu,
R.T.Cass.
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Ref.
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j am chem soc, 1996,
118,
7914.
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Secondary reference #2
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Title
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Preparation of a protein-Dimerizing ligand by topochemistry and structure-Based design
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Author
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B.A.Katz.
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Ref.
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j am chem soc, 1996,
118,
2535.
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Secondary reference #3
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Title
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Topochemical catalysis achieved by structure-Based ligand design.
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Authors
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B.A.Katz,
R.T.Cass,
B.Liu,
R.Arze,
N.Collins.
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Ref.
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J Biol Chem, 1995,
270,
31210-31218.
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PubMed id
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Secondary reference #4
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Title
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Topochemistry for preparing ligands that dimerize receptors.
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Authors
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B.A.Katz,
R.M.Stroud,
N.Collins,
B.Liu,
R.Arze.
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Ref.
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Chem Biol, 1995,
2,
591-600.
[DOI no: ]
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PubMed id
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Secondary reference #5
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Title
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Binding to protein targets of peptidic leads discovered by phage display: crystal structures of streptavidin-Bound linear and cyclic peptide ligands containing the hpq sequence.
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Author
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B.A.Katz.
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Ref.
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Biochemistry, 1995,
34,
15421-15429.
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PubMed id
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Secondary reference #6
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Title
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Structure-Based design of high affinity streptavidin binding cyclic peptide ligands containing thioether cross-Links
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Authors
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B.A.Katz,
C.R.Johnson,
R.T.Cass.
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Ref.
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j am chem soc, 1995,
117,
8541.
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