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PDBsum entry 2v1v
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Hydrolase inhibitor
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PDB id
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2v1v
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References listed in PDB file
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Key reference
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Title
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Conservative mutation met8 --≫ leu affects the folding process and structural stability of squash trypsin inhibitor cmti-I.
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Authors
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I.Zhukov,
L.Jaroszewski,
A.Bierzyński.
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Ref.
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Protein Sci, 2000,
9,
273-279.
[DOI no: ]
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PubMed id
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Abstract
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Protein molecules can accommodate a large number of mutations without noticeable
effects on their stability and folding kinetics. On the other hand, some
mutations can have quite strong effects on protein conformational properties.
Such mutations either destabilize secondary structures, e.g., alpha-helices, are
incompatible with close packing of protein hydrophobic cores, or lead to
disruption of some specific interactions such as disulfide cross links, salt
bridges, hydrogen bonds, or aromatic-aromatic contacts. The Met8 --> Leu
mutation in CMTI-I results in significant destabilization of the protein
structure. This effect could hardly be expected since the mutation is highly
conservative, and the side chain of residue 8 is situated on the protein
surface. We show that the protein destabilization is caused by rearrangement of
a hydrophobic cluster formed by side chains of residues 8, Ile6, and Leu17 that
leads to partial breaking of a hydrogen bond formed by the amide group of Leu17
with water and to a reduction of a hydrophobic surface buried within the
cluster. The mutation perturbs also the protein folding. In aerobic conditions
the reduced wild-type protein folds effectively into its native structure,
whereas more then 75% of the mutant molecules are trapped in various misfolded
species. The main conclusion of this work is that conservative mutations of
hydrophobic residues can destabilize a protein structure even if these residues
are situated on the protein surface and partially accessible to water.
Structural rearrangement of small hydrophobic clusters formed by such residues
can lead to local changes in protein hydration, and consequently, can affect
considerably protein stability and folding process.
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Secondary reference #1
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Title
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The analysis of molecular dynamics for m8l cmti-I protein
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Authors
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P.Sledz,
I.Zhukov,
A.Ejchart.
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Ref.
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TO BE PUBLISHED ...
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