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PDBsum entry 1bsd
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* Residue conservation analysis
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J Mol Biol
234:847-860
(1993)
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PubMed id:
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Crystal structural analysis of mutations in the hydrophobic cores of barnase.
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A.M.Buckle,
K.Henrick,
A.R.Fersht.
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ABSTRACT
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We have solved and analysed the crystal structures of five mutants in the
hydrophobic core of barnase to investigate the structural basis for the
contribution of hydrophobic residues and side-chain packing to the stability of
globular proteins. In case ease, an amino acid side-chain has been replaced with
one of smaller volume. The overall structures of four Ile-->Val mutants
(residues 51, 76, 88 and 96) and one Leu-->Val mutant (residue 89) are all
isomorphous with the wild-type structure. The magnitude and nature of structural
shifts in the three hydrophobic core regions of barnase depend on the local
environment of the substitution site, but have some features in common. (1)
Side-chain atoms move to a greater extent than do main-chain atoms. (2)
Repacking at the substitution site is achieved by either a rigid body shift of
side-chain atoms (for Ile-->Val76 and Ile-->Val96 mutants), or by a
combination of a side-chain shift and rotation (for Ile-->Val51 and
Ile-->Val88 mutants). The mutated residue moves to the greatest extent, and
generally in the direction of the created cavity (the largest atomic shift is
0.9 A, for Ile-->Val51). The space left behind from such shifts is not seen
to be filled by neighbouring side-chains. (3) Where a cavity remains after
mutation, it does not contain any solvent molecules. (4) There is no correlation
between the extent of structural movements and the atomic temperature factors of
atoms that have moved. (5) Structural movements are not large enough to disrupt
hydrogen bonding. Valine 88, in the Ile-->Val88 mutant, is disordered and the
electron density suggests several side-chain conformations. The reduction in the
volumes of the cavities introduced upon mutation, due to collapse of the
surrounding structure, ranges from 11% (Ile-->Val96) to 90% (Ile-->Val51).
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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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A.C.Joerger,
and
A.R.Fersht
(2007).
Structure-function-rescue: the diverse nature of common p53 cancer mutants.
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Oncogene,
26,
2226-2242.
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A.C.Joerger,
H.C.Ang,
and
A.R.Fersht
(2006).
Structural basis for understanding oncogenic p53 mutations and designing rescue drugs.
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Proc Natl Acad Sci U S A,
103,
15056-15061.
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PDB codes:
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K.Ohno,
and
M.Sakurai
(2006).
Linear-scaling molecular orbital calculations for the pKa values of ionizable residues in proteins.
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J Comput Chem,
27,
906-916.
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M.Bueno,
L.A.Campos,
J.Estrada,
and
J.Sancho
(2006).
Energetics of aliphatic deletions in protein cores.
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Protein Sci,
15,
1858-1872.
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M.L.Quillin,
P.T.Wingfield,
and
B.W.Matthews
(2006).
Determination of solvent content in cavities in IL-1beta using experimentally phased electron density.
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Proc Natl Acad Sci U S A,
103,
19749-19753.
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PDB code:
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P.Cioni
(2006).
Role of protein cavities on unfolding volume change and on internal dynamics under pressure.
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Biophys J,
91,
3390-3396.
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D.Segal,
and
M.Eisenstein
(2005).
The effect of resolution-dependent global shape modifications on rigid-body protein-protein docking.
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Proteins,
59,
580-591.
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K.Kamada,
and
F.Hanaoka
(2005).
Conformational change in the catalytic site of the ribonuclease YoeB toxin by YefM antitoxin.
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Mol Cell,
19,
497-509.
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PDB codes:
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S.Park,
and
J.G.Saven
(2005).
Statistical and molecular dynamics studies of buried waters in globular proteins.
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Proteins,
60,
450-463.
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A.Berchanski,
B.Shapira,
and
M.Eisenstein
(2004).
Hydrophobic complementarity in protein-protein docking.
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Proteins,
56,
130-142.
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M.J.Lachenmann,
J.E.Ladbury,
X.Qian,
K.Huang,
R.Singh,
and
M.A.Weiss
(2004).
Solvation and the hidden thermodynamics of a zinc finger probed by nonstandard repair of a protein crevice.
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Protein Sci,
13,
3115-3126.
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PDB code:
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S.Ventura,
and
L.Serrano
(2004).
Designing proteins from the inside out.
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Proteins,
56,
1.
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T.J.Magliery,
and
L.Regan
(2004).
Combinatorial approaches to protein stability and structure.
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Eur J Biochem,
271,
1595-1608.
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R.Rodríguez-López,
A.Osorio,
L.Sánchez-Pulido,
M.De La Hoya,
A.Barroso,
T.Caldés,
and
J.Benítez
(2003).
No mutations in the XRCC2 gene in BRCA1/2-negative high-risk breast cancer families.
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Int J Cancer,
103,
136-137.
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S.R.Brych,
J.Kim,
T.M.Logan,
and
M.Blaber
(2003).
Accommodation of a highly symmetric core within a symmetric protein superfold.
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Protein Sci,
12,
2704-2718.
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PDB codes:
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T.Wang,
and
R.C.Wade
(2003).
Implicit solvent models for flexible protein-protein docking by molecular dynamics simulation.
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Proteins,
50,
158-169.
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A.A.Gorfe,
P.Ferrara,
A.Caflisch,
D.N.Marti,
H.R.Bosshard,
and
I.Jelesarov
(2002).
Calculation of protein ionization equilibria with conformational sampling: pK(a) of a model leucine zipper, GCN4 and barnase.
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Proteins,
46,
41-60.
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A.Heifetz,
E.Katchalski-Katzir,
and
M.Eisenstein
(2002).
Electrostatics in protein-protein docking.
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Protein Sci,
11,
571-587.
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J.Funahashi,
K.Takano,
Y.Yamagata,
and
K.Yutani
(2002).
Positive contribution of hydration structure on the surface of human lysozyme to the conformational stability.
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J Biol Chem,
277,
21792-21800.
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PDB codes:
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R.E.Georgescu,
E.G.Alexov,
and
M.R.Gunner
(2002).
Combining conformational flexibility and continuum electrostatics for calculating pK(a)s in proteins.
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Biophys J,
83,
1731-1748.
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S.B.Nolde,
A.S.Arseniev,
V.Y.Orekhov,
and
M.Billeter
(2002).
Essential domain motions in barnase revealed by MD simulations.
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Proteins,
46,
250-258.
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S.Chakravarty,
A.Bhinge,
and
R.Varadarajan
(2002).
A procedure for detection and quantitation of cavity volumes proteins. Application to measure the strength of the hydrophobic driving force in protein folding.
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J Biol Chem,
277,
31345-31353.
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J.W.O'Neill,
D.E.Kim,
D.Baker,
and
K.Y.Zhang
(2001).
Structures of the B1 domain of protein L from Peptostreptococcus magnus with a tyrosine to tryptophan substitution.
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Acta Crystallogr D Biol Crystallogr,
57,
480-487.
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PDB codes:
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R.B.Best,
B.Li,
A.Steward,
V.Daggett,
and
J.Clarke
(2001).
Can non-mechanical proteins withstand force? Stretching barnase by atomic force microscopy and molecular dynamics simulation.
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Biophys J,
81,
2344-2356.
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E.J.Sundberg,
M.Urrutia,
B.C.Braden,
J.Isern,
D.Tsuchiya,
B.A.Fields,
E.L.Malchiodi,
J.Tormo,
F.P.Schwarz,
and
R.A.Mariuzza
(2000).
Estimation of the hydrophobic effect in an antigen-antibody protein-protein interface.
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Biochemistry,
39,
15375-15387.
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PDB codes:
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H.Kono,
M.Saito,
and
A.Sarai
(2000).
Stability analysis for the cavity-filling mutations of the Myb DNA-binding domain utilizing free-energy calculations.
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Proteins,
38,
197-209.
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J.Funahashi,
K.Takano,
Y.Yamagata,
and
K.Yutani
(2000).
Role of surface hydrophobic residues in the conformational stability of human lysozyme at three different positions.
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Biochemistry,
39,
14448-14456.
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PDB codes:
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P.V.Nikolova,
K.B.Wong,
B.DeDecker,
J.Henckel,
and
A.R.Fersht
(2000).
Mechanism of rescue of common p53 cancer mutations by second-site suppressor mutations.
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EMBO J,
19,
370-378.
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V.Gaponenko,
J.W.Howarth,
L.Columbus,
G.Gasmi-Seabrook,
J.Yuan,
W.L.Hubbell,
and
P.R.Rosevear
(2000).
Protein global fold determination using site-directed spin and isotope labeling.
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Protein Sci,
9,
302-309.
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C.Martin,
V.Richard,
M.Salem,
R.Hartley,
and
Y.Mauguen
(1999).
Refinement and structural analysis of barnase at 1.5 A resolution.
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Acta Crystallogr D Biol Crystallogr,
55,
386-398.
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PDB code:
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R.Loris,
U.Langhorst,
S.De Vos,
K.Decanniere,
J.Bouckaert,
D.Maes,
T.R.Transue,
and
J.Steyaert
(1999).
Conserved water molecules in a large family of microbial ribonucleases.
|
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Proteins,
36,
117-134.
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PDB codes:
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V.De Filippis,
F.De Antoni,
M.Frigo,
P.Polverino de Laureto,
and
A.Fontana
(1998).
Enhanced protein thermostability by Ala-->Aib replacement.
|
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Biochemistry,
37,
1686-1696.
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Y.Yamagata,
M.Kubota,
Y.Sumikawa,
J.Funahashi,
K.Takano,
S.Fujii,
and
K.Yutani
(1998).
Contribution of hydrogen bonds to the conformational stability of human lysozyme: calorimetry and X-ray analysis of six tyrosine --> phenylalanine mutants.
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Biochemistry,
37,
9355-9362.
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PDB codes:
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A.Akasako,
M.Haruki,
M.Oobatake,
and
S.Kanaya
(1997).
Conformational stabilities of Escherichia coli RNase HI variants with a series of amino acid substitutions at a cavity within the hydrophobic core.
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J Biol Chem,
272,
18686-18693.
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K.Takano,
Y.Yamagata,
S.Fujii,
and
K.Yutani
(1997).
Contribution of the hydrophobic effect to the stability of human lysozyme: calorimetric studies and X-ray structural analyses of the nine valine to alanine mutants.
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Biochemistry,
36,
688-698.
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PDB codes:
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R.R.Gabdoulline,
and
R.C.Wade
(1997).
Simulation of the diffusional association of barnase and barstar.
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Biophys J,
72,
1917-1929.
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A.M.Buckle,
P.Cramer,
and
A.R.Fersht
(1996).
Structural and energetic responses to cavity-creating mutations in hydrophobic cores: observation of a buried water molecule and the hydrophilic nature of such hydrophobic cavities.
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Biochemistry,
35,
4298-4305.
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PDB codes:
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B.A.Fields,
F.A.Goldbaum,
W.Dall'Acqua,
E.L.Malchiodi,
A.Cauerhff,
F.P.Schwarz,
X.Ysern,
R.J.Poljak,
and
R.A.Mariuzza
(1996).
Hydrogen bonding and solvent structure in an antigen-antibody interface. Crystal structures and thermodynamic characterization of three Fv mutants complexed with lysozyme.
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Biochemistry,
35,
15494-15503.
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PDB codes:
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E.S.Eberhardt,
P.K.Wittmayer,
B.M.Templer,
and
R.T.Raines
(1996).
Contribution of a tyrosine side chain to ribonuclease A catalysis and stability.
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Protein Sci,
5,
1697-1703.
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M.Oliveberg,
and
A.R.Fersht
(1996).
New approach to the study of transient protein conformations: the formation of a semiburied salt link in the folding pathway of barnase.
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Biochemistry,
35,
6795-6805.
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S.Ganguli,
H.Wang,
P.Matsumura,
and
K.Volz
(1995).
Uncoupled phosphorylation and activation in bacterial chemotaxis. The 2.1-A structure of a threonine to isoleucine mutant at position 87 of CheY.
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J Biol Chem,
270,
17386-17393.
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PDB code:
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E.P.Baldwin,
and
B.W.Matthews
(1994).
Core-packing constraints, hydrophobicity and protein design.
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Curr Opin Biotechnol,
5,
396-402.
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Y.Harpaz,
M.Gerstein,
and
C.Chothia
(1994).
Volume changes on protein folding.
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Structure,
2,
641-649.
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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
codes are
shown on the right.
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Links
