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1. |
The neuraminidase of influenza virus |
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Proteins: Structure, Function, and Bioinformatics,
Volume 6,
Issue 4,
1989,
Page 341-356
Gillian M. Air,
W. Graeme Laver,
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摘要:
AbstractIt is the enzyme neuraminidase, projecting form the surface of influenza virus particles, which allows the virus to leave infected cells and spread in the body. Antibodies which inhibit the enzyme limit the infection, but antigenic variation of the neuraminidase renders it ineffective in a vaccine. This article describes the crystal structure of influenza virus neuraminidase, information about the active site which may lead to development of specific and effective inhibitors of the enzyme, and the structure of epitopes (antigenic determinants) on the neuraminidase. The 3‐dimensional structure of the epitopes was obtained by X‐ray diffraction methods using crystals of neuraminidase complexed with monoclonal antibody Fab fragments. Escape mutants, selected by growing virus in the presence of monoclonal antibodies to the neuraminidase, possess single amino acid sequence changes. The crystal structure of two mutants showed that the change in structure was restricted to that particular sidechain, but the change in the epitope was sufficient to abolish antibody binding even though it is known in one case that 21 other amino acids on the neuraminidase are in contact with the antib
ISSN:0887-3585
DOI:10.1002/prot.340060402
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
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2. |
Three‐dimensional structure of the neurotoxin ATX Ia fromAnemonia sulcatain aqueous solution determined by nuclear magnetic resonance spectroscopy |
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Proteins: Structure, Function, and Bioinformatics,
Volume 6,
Issue 4,
1989,
Page 357-371
Hans Widmer,
Martin Billeter,
Kurt Wüthrich,
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摘要:
AbstractWith the aid of1H nuclear magnetic resonance (NMR) spectroscopy, the three‐dimensional structure in aqueous solution was determined for ATX Ia, which is a 46 residue polypeptide neurotoxin of the sea anemoneAnemonia sulcata. The input for the structure calculations consisted of 263 distance constraints from nuclear Overhauser effects (NOE) and 76 vicinal coupling constants. For the structure calculation several new or ammended programs were used in a revised strategy consisting of five successive computational steps. First, the program HABAS was used for a complete search of all backbone and χ1conformations that are compatible with the intraresidual and sequential NMR constraints. Second, using the program DISMAN, we extended this approach to pentapeptides by extensive sapling of al conformations that are consistent with the local and medium‐range NMR constraints. Both steps resulted in the definition of additional dihedral angle constraints and in stereospecific assignments for a number of β‐methylene groups. In the next two steps DISMAN was used to obtain a group of eight conformers that contain no significant residual violations of the NMR constraints or van der Waals contacts. Finally, these structures were subjected to restrained energy refinement with a modified version of the molecular mechanics module of AMBER, which in addition to the energy force field includes potentials for the NOCE distance constraints and the dihedral angle constraints. The average of the pairwise minimal RMS distances between the resulting refined conformers calculated for the well defined molecular core, which contains the backbone atoms of 35 residues and 20 interior side chains, is 1.5 ± 0.3 Å. This core is formed by a four‐stranded β‐sheet connected by two well‐defined loops, and there is an additional flexible loop consisting of the eleven residues 8‐18. The core of the protein is stabilized by three disulfide bridges, which are surrounded by hydrophobic residues and shielded on one side by hy
ISSN:0887-3585
DOI:10.1002/prot.340060403
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
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3. |
Deletions and replacements of omega loops in yeast iso‐1‐cytochromec |
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Proteins: Structure, Function, and Bioinformatics,
Volume 6,
Issue 4,
1989,
Page 372-381
Jacquelyn S. Fetrow,
Thomas S. Cardillo,
Fred Sherman,
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摘要:
AbstractΩ(Omega)‐loops are protein secondary structural elements having small distance between segment termini. It should be possible to delete or replace certain of these Ω‐loops without greatly distorting the overall structure of the remaining portion of the molecule. Functional requirements of regions of iso‐1‐cytochromecfrom the yeastSaccharomyces cerevisiaewere in investigated by determining the biosynthesis and activity in vivo of mutant forms in which four different Ω‐loops were individually deleted, or in which one Ω‐loop was replaced with five different segments. Deletion encompassing amino acid positions 27–33 and79–83 either prevented synthesis of the holoprotein, or produced highly labile iso‐1‐cytochromesc, whereas deletions encompassing position 42–45 and 48–55 allowed partial synthesis and activity. These two latter regions, therefore, are not absolutely required for any biosynthetic process such as heme attachment, mitochondrial import, or for enzymatic interactions. All replacements in Loop A (residue position 24–33) with the same size (10 amino acid residues), longer (13 and 15 amino acid residues), or shorter segments (6 amino acid residues), resulted in strains having at least partial levels of iso‐1‐cytochromec; however, the relative activities ranged from zero to almost the normal level. Thus, Loop A does not appear to be essential for such biosynthetic steps as heme attachment and mitochondrial import. In contrast, the full range of relative activities suggest that this region interacts with physiological partners to carry
ISSN:0887-3585
DOI:10.1002/prot.340060404
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
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4. |
Structural determinants of the conformations of medium‐sized loops in proteins |
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Proteins: Structure, Function, and Bioinformatics,
Volume 6,
Issue 4,
1989,
Page 382-394
Anna Tramontano,
Cyrus Chothia,
Arthur M. Lesk,
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摘要:
AbstractLoops are integral components of protein structures, providing links between elements of secondary structure, and in many cases contributing to catalytic and binding sites.The conformations of short loops are now understood to depend primarily on their amino acid sequences. In contrast, the structural determinants of longer loops involve hydrogen‐bonding and packing interactions within the loop and with other parts of the protein. By searching solved protein structures for regions similar in main chain conformation to the antigen‐binding loops in immunoglobulins, we identified medium‐sized loops of similar structure in unrelated proteins, and compared the determinants of their conformations.For loops that form compact substructures the major determinant of the conformation is the formation of hydrogen bonds to inward‐pointing main chain atoms. For oops that have more extended conformations, the major determinant of their structure is the packing of a particular residue or residues against the rest of the protein.The following picture emerges: Medium‐sized lops of similar conformation are stabilized by similar interaction. The groups that interact with the loop have very similar spatial dispositions with respect to the loop. However, the residues that provide these interactions may arise from dissimilar parts of the protein: The conformation of the loop requires certain interactions that the protein may provide in a variet
ISSN:0887-3585
DOI:10.1002/prot.340060405
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
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5. |
Alternate succession of steps can lead to the folding of a multidomain oligomeric protein |
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Proteins: Structure, Function, and Bioinformatics,
Volume 6,
Issue 4,
1989,
Page 395-404
Anne Murry‐Brelier,
Michel E. Goldberg,
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摘要:
AbstractThe β2subunit ofEscherichia colitryptophan synthase can be either unfolded in 6 M guanidine, or extensively denatured at acidic pH. These two denatured form of β2have different circular dichroism spectra and thus correspond to distinct physical states. Here we compare the folding pathways of these two different denatured forms of β chains. We describe the kinetics of regain of a variety of physical, functional, ad immunochemical signals characteristic of six successive steps previously identified on the folding pathway of guanidine unfolded β2. It is shown that whereas identical molecular events over with the same kinetics, the two folding pathways are different, and involve different structural intermedia
ISSN:0887-3585
DOI:10.1002/prot.340060406
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
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6. |
Use of restrained molecular dynamics in water to determine three‐dimensional protein structure: Prediction of the three‐dimensional structure ofEcballium elateriumtrypsin inhibitor II |
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Proteins: Structure, Function, and Bioinformatics,
Volume 6,
Issue 4,
1989,
Page 405-417
Laurent Chiche,
Christine Gaboriaud,
Annie Heitz,
Jean‐Paul Mornon,
Bertrand Castro,
Peter A. Kollman,
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摘要:
AbstractRefinement of distance geometry (DG) structures of EETI‐II (Heitz et al.:Biochemistry28:2392–2398, 1989), a member of the squash family trypsin inhibitor, have been carried out by restrained molecular dynamics (RMD) in water. The resulting models show better side chain apolar/polar surface ratio and estimated solvation free energy than structures refined “in cacuo.” The consistent lower values of residual NMR constraint violations, apolar/polar surface ration and solvation free energy of one of these refined structures allowed prediction of the 3D folding and disulfide connectivity of EETI‐II. Except for the few first residues for which no NMR constraints were available, this computer model fully agree with X‐ray structures of CMTI‐I (Boe et al.:FEBS Lett.242:285–292, 1989) and EETI‐II complexed with trypsin that appeared after the RMD simulation was completed. Restrained molecular dynamics n water is thus proved to highly valuable for refinement of DG structures Also, the successful use of apolar/polar surface ratio and solvation free energy reinforce the analysis of Novotny et al. (Proteins4: 19–30, 1988) and shows that these criteria are useful indicators of correct vers
ISSN:0887-3585
DOI:10.1002/prot.340060407
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
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7. |
The surface area of monomeric proteins: Significance of power law behavior |
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Proteins: Structure, Function, and Bioinformatics,
Volume 6,
Issue 4,
1989,
Page 418-423
Stephen H. Bryant,
Suhail A. Islam,
David L. Weaver,
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摘要:
AbstractThe coefficients in a power low fit of accessible area versus molecular weight for high‐reslution monomeric protein structures are assessed with respect to statistical accuracy using bootstrap analyses, and with respect to physical significance using model systems and the concept of roughness or fractal structure of the protein surfac
ISSN:0887-3585
DOI:10.1002/prot.340060408
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
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8. |
Acid‐induced dimerization of skeletal troponin C |
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Proteins: Structure, Function, and Bioinformatics,
Volume 6,
Issue 4,
1989,
Page 424-430
Chien‐Kao Wang,
Jacob Lebowitz,
Herbert C. Cheung,
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摘要:
AbstractWe have investigated pH‐dependent changes of the properties of troponin C from rabbit skeletal muscle. At pH 7.5 this protein is a monomer and at pH 5.2 it is a dimer. In contrast, bovine cardiac troponin C remains essentially monomeric at pH 5.2. Bovine brain calmodulin is not a dimer, but significantly aggregated at the same acidic pH. The dimerization of skeletal troponin C was demonstrated by low‐speed (16,000 rpm) sedimentation equilibrium measurements carried out at 20°C and by polyacrylamide gel electrophoresis under nondenaturing conditions. Dimer formation was significantly inhibited in the ultracentrifuge at rotor speeds of 30,000 and 40,000 rpm at 20°C, and was completely prevented at a rotor speed of 40,000 rpm and 4°C. This temperature and pressure dependence of dimerization strongly suggests that hydrophobic bonding is a major factor in promoting skeletal troponin C association at pH 5.2. The intramolecular distance between Met‐25 and Cys‐98 of rabbit skeletal troponin C deduced from fluorescence resonance energy transfer measurements increased by a factor of two upon lowering the pH from 7.5 to 5.2, indicating a pH‐dependent transition in which the protein changed from a relatively compact conformation to an elongated conformation. The protein‐induced increase in the energy transfer distance is related to the acid‐induced dimerization of the protein. The extended conformation observed at pH 5.2 is compatible with the dumbbell‐shaped structure of skeletal troponin C crystals obtained from turkey at pH 5.0 [Herzberg, O., James, M. N. G. Nature (London) 313:653–659, 1985] and chicken at pH 5.1 (Sundaralingam, M., Bergstrome, R., Strasburg, G., Rao, S. T., Roychowdhury, P., Greaser, M., Wang, B. C. Science 227:945–948, 1985). However, the conformation in neural solution deviates form that predicted by crystallography. Intermolecular interactions leading to dimer formation likely play an important role in promoting the extended conformation th
ISSN:0887-3585
DOI:10.1002/prot.340060409
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
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9. |
Masthead |
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Proteins: Structure, Function, and Bioinformatics,
Volume 6,
Issue 4,
1989,
Page -
Preview
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PDF (128KB)
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ISSN:0887-3585
DOI:10.1002/prot.340060401
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
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