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PDBsum entry 4ge0
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Unknown function
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PDB id
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4ge0
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References listed in PDB file
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Key reference
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Title
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Influence of peptide dipoles and hydrogen bonds on reactive cysteine pka values in fission yeast dj-1.
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Authors
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P.Madzelan,
T.Labunska,
M.A.Wilson.
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Ref.
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Febs J, 2012,
279,
4111-4120.
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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 have
been manually determined.
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Abstract
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Cysteine residues with depressed pK(a) values are critical for the functions of
many proteins. Several types of interactions can stabilize cysteine thiolate
anions, including hydrogen bonds between thiol(ate)s and nearby residues as well
as electrostatic interactions involving charged residues or dipoles. Dipolar
stabilization of thiolates by peptide groups has been suggested to play a
particularly important role near the N-termini of α-helices. Using a
combination of X-ray crystallography, site-directed mutagenesis and
spectroscopic methods, we show that the reactive cysteine residue (Cys111) in
Schizosaccharomyces pombe DJ-1 experiences a 0.6 unit depression of its thiol
pK(a) as a consequence of a hydrogen bond donated by a threonine side chain
(Thr114) to a nearby peptide carbonyl oxygen at the N-terminus of an α-helix.
This extended hydrogen bonded interaction is consistent with a sum of dipoles
model whereby the distal hydrogen bond polarizes and strengthens the direct
hydrogen bond between the proximal amide hydrogen and the cysteine thiol(ate).
Therefore, our results suggest that the local dipolar enhancement of hydrogen
bonds can appreciably stabilize cysteine thiolate formation. However, the
substitution of a valine residue with a proline at the i + 3 position has only
a minor effect (0.3 units) on the pK(a) of Cys111. As proline has a reduced
peptide dipole moment, this small effect suggests that a more extended helix
macrodipolar effect does not play a major role in this system. DATABASE:
Structural models and diffraction data are available in the Protein Data Bank
under the accession number(s) 4GDH (wild-type SpDJ-1), 4GE0 (T114P SpDJ-1) and
4GE3 (T114V SpDJ-1) STRUCTURED DIGITAL ABSTRACT:
SpDJ-1 and SpDJ-1 bind by x-ray crystallography (View interaction).
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