Biomedical subjects

G D Brayer

Publications and source records attributed to G D Brayer.

At least 55 records · Page 3Linked to original sources

PubMed1991

Enhanced thermodynamic stabilities of yeast iso-1-cytochromes c with amino acid replacements at positions 52 and 102.

We have determined the structures and thermodynamic stabilities of the wild type Asn-52 and unusually thermostable mutant Ile-52 yeast iso-1-cytochromes c (Das, G., Hickey, D. R. McLendon, D., McLendon, G., and Sherman, F. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 496-499). Although both structures were similar, Water-166, buried within the wild type protein, is excluded from the Ile-52 mutant, which substantially reorganizes the local hydrogen bonding. Wild type Cys-102 was replaced with alanine or serine to eliminate dimerization in vitro. The Cys-102 (wild type), Ala-102, and Ser-102 proteins were equally stable, whereas the chemically modified Cys-102-SCH3 was less stable. The order of stability observed with replacements at positions 52 and 102 was as follows: Ile-52 Ala-102 greater than Ala-52 Ala-102 greater than Asn-52 Ala-102 ("normal") greater than Gly-52 Ala-102. No significant stabilization was attributed to potential energy interactions expressed as helix-forming propensities of replacements at position 52. A high correlation between differences in free energy changes and transfer free energies suggests hydrophobic interactions are the main factor for enhancing stability in the Ile-52 mutant. Additional possible contributions to the thermostability of the Ile-52 variant are energetic effects due to packing and hydrogen bonding changes surrounding position 52.

Amino Acids↗

PubMed1990

High-resolution refinement of yeast iso-1-cytochrome c and comparisons with other eukaryotic cytochromes c.

The structure of yeast iso-1-cytochrome c has been refined against X-ray diffraction data to a nominal resolution of 1.23 A. The atomic model contains 893 protein atoms, as well as 116 water molecules and one sulfate anion. Also included in the refinement are 886 hydrogen atoms belonging to the protein molecule. The crystallographic R-factor is 0.192 for the 12,513 reflections with F greater than or equal to 3 sigma (F) in the resolution range 6.0 to 1.23 A. Co-ordinate accuracy is estimated to be better than 0.18 A. The iso-1-cytochrome c molecule has the typical cytochrome c fold, with the polypeptide chain organized into a series of alpha-helices and reverse turns that serve to envelop the heme prosthetic group in a hydrophobic pocket. Inspection of the conformations of helices in the molecule shows that the local environments of the helices, in particular the presence of intrahelical threonine residues, cause distortions from ideal alpha-helical geometry. Analysis of the internal mobility of iso-1-cytochrome c, based on refined crystallographic temperature factors, shows that the most rigid parts of the molecule are those that are closely associated with the heme group. The degree of saturation of hydrogen-bonding potential is high, with 90% of all polar atoms found to participate in hydrogen bonding. The geometry of intramolecular hydrogen bonds is typical of that observed in other high-resolution protein structures. The 116 water molecules present in the model represent about 41% of those expected to be present in the asymmetric unit. The majority of the water molecules are organized into a small number of hydrogen-bonding networks that are anchored to the protein surface. Comparison of the structure of yeast iso-1-cytochrome c with those of tuna and rice cytochromes c shows that these three molecules have very high structural similarity, with the atomic packing in the heme crevice region being particularly highly conserved. Large conformational differences that are observed between these cytochromes c can be explained by amino acid substitutions. Additional subtle differences in the positioning of the side-chains of several highly conserved residues are also observed and occur due to unique features in the local environments of each cytochrome c molecule.(ABSTRACT TRUNCATED AT 400 WORDS)

Crystallization↗

PubMed1990

High-resolution three-dimensional structure of horse heart cytochrome c.

The 1.94 A resolution three-dimensional structure of oxidized horse heart cytochrome c has been elucidated and refined to a final R-factor of 0.17. This has allowed for a detailed assessment of the structural features of this protein, including the presence of secondary structure, hydrogen-bonding patterns and heme geometry. A comprehensive analysis of the structural differences between horse heart cytochrome c and those other eukaryotic cytochromes c for which high-resolution structures are available (yeast iso-1, tuna, rice) has also been completed. Significant conformational differences between these proteins occur in three regions and primarily involve residues 22 to 27, 41 to 43 and 56 to 57. The first of these variable regions is part of a surface beta-loop, whilst the latter two are located together adjacent to the heme group. This study also demonstrates that, in horse cytochrome c, the side-chain of Phe82 is positioned in a co-planar fashion next to the heme in a conformation comparable to that found in other cytochromes c. The positioning of this residue does not therefore appear to be oxidation-state-dependent. In total, five water molecules occupy conserved positions in the structures of horse heart, yeast iso-1, tuna and rice cytochromes c. Three of these are on the surface of the protein, serving to stabilize local polypeptide chain conformations. The remaining two are internally located. One of these mediates a charged interaction between the invariant residue Arg38 and a nearby heme propionate. The other is more centrally buried near the heme iron atom and is hydrogen bonded to the conserved residues Asn52, Tyr67 and Thr78. It is shown that this latter water molecule shifts in a consistent manner upon change in oxidation state if cytochrome c structures from various sources are compared. The conservation of this structural feature and its close proximity to the heme iron atom strongly implicate this internal water molecule as having a functional role in the mechanism of action of cytochrome c.

Amino Acid Sequence↗

PubMed1990

High-resolution study of the three-dimensional structure of horse heart metmyoglobin.

The three-dimensional structure of horse heart metmyoglobin has been refined to a final R-factor of 15.5% for all observed data in the 6.0 to 1.9 A resolution range. The final model consists of 1242 non-hydrogen protein atoms, 154 water molecules and one sulfate ion. This structure has nearly ideal bonding and bond angle geometry. A Luzzati plot of the variation in R-factor with resolution yields an estimated mean co-ordinate error of 0.18 A. An extensive analysis of the pattern of hydrogen bonds formed in horse heart metmyoglobin has been completed. Over 80% of the polypeptide chain is involved in eight helical segments, of which seven are composed mainly of alpha-helical (3.6(13))-type hydrogen bonds; the remaining helix is composed entirely of 3(10) hydrogen bonds. Altogether, of 102 hydrogen bonds between main-chain atoms only six are not involved in helical structures, and four of these six occur within beta-turns. The majority of water molecules in horse heart metmyoglobin are found in solvent networks that range in size from two to 35 members. The size of water molecule networks can be rationalized on the basis of three factors: the number of hydrogen bonds to the protein surface, the presence of charged side-chain atoms, and the ability to bridge to neighboring molecules in the crystal lattice. Bridging water networks form the dominant intermolecular interactions. The backbone conformation of horse heart metmyoglobin is very similar to sperm whale metmyoglobin, with significant differences in secondary structure occurring only near residues 119 and 120, where residues 120 to 123 in sperm whale form a distorted type I reverse turn and the horse heart protein has a type II turn at residues 119 to 122. Nearly all of the hydrogen bonds between main-chain atoms (occurring mainly in helical regions) are common to both proteins, and more than half of the hydrogen bonds involving side-chain atoms observed in horse heart are also found in sperm whale metmyoglobin. Unlike sperm whale metmyoglobin, the heme iron atom in horse heart metmyoglobin is not significantly displaced from the plane of the heme group.

Animals↗

PubMed1990

Mutagenic, electrochemical, and crystallographic investigation of the cytochrome b5 oxidation-reduction equilibrium: involvement of asparagine-57, serine-64, and heme propionate-7.

A gene coding for lipase-solubilized bovine liver microsomal cytochrome b5 has been synthesized, expressed in Escherichia coli, and mutated at functionally critical residues. Characterization of the recombinant protein revealed that it has a reduction potential that is approximately 17 mV lower than that of authentic wild-type protein at pH 7 (25 degrees C). Structural studies determined that the recombinant protein differed in sequence from authentic wild-type cytochrome b5 owing to three errors in amidation status in the published sequence for the protein on which the gene synthesis was based. The structural origin of the lower reduction potential exhibited by the triple mutant has been investigated through X-ray crystallographic determination of the three-dimensional structure of this protein and is attributed to the presence of Asp-57 within 3.3 A of heme vinyl-4 in the mutant. In addition, the model developed by Argos and Mathews [Argos, P., & Mathews, F.S. (1975) J. Biol. Chem. 250, 747] for the change in cytochrome b5 oxidation state has been studied through mutation of Ser-64 to Ala. In this model, Ser-64 is postulated to stabilize the oxidized protein through H-bonding interactions with heme propionate-7 that orients this propionate group 6.2 A from the heme iron. Spectroelectrochemical studies of a mutant in which Ser-64 has been changed to an alanyl residue demonstrate that this protein has a reduction potential that is 7 mV lower than that of the wild-type protein; moreover, conversion of the heme propionate groups to the corresponding methyl esters increases the potential by 67 mV.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1989

A polypeptide chain-refolding event occurs in the Gly82 variant of yeast iso-1-cytochrome c.

The replacement of Phe82 in yeast iso-1-cytochrome c by a glycine residue substantially alters both the tertiary structure and electron transfer properties of this protein. The largest structural change involves a polypeptide chain refolding of residues 79 through 85. Refolding places glycines 82, 83 and 84 immediately adjacent to the plane of the heme group in a spatial positioning comparable to that of the phenyl ring of Phe82 in the wild-type protein. Despite this perturbation in structure, solvent accessibility computations show that heme solvent exposure has not increased in the Gly82 variant protein. However, refolding does result in the introduction of a number of polar groups into the hydrophobic heme pocket. This appears to be responsible for the decreased reduction potential of the heme in this protein. The present study, along with that of the Ser82 variant protein (Louie et al., 1988b), clearly establishes the link between dielectric constant within the heme crevice and reduction potential. The further anomalously low electron transfer activity of the Gly82 variant protein would appear to arise from two factors. First, the polypeptide chain medium now adjacent to the heme is unable to facilitate electron transfer in a manner similar to that of the aromatic side-chain of Phe82. Second, polypeptide chain refolding significantly alters the surface contour of the Gly82 protein rendering it less suitable to interact with the corresponding complementary surfaces of redox partners. Our data support the conclusion that Phe82 plays a number of roles in the electron transfer process mediated by yeast iso-1-cytochrome c. These include the maintenance of the heme environment, provision of an optimal medium along the path of electron transfer and formation of interactions at the contact interface in complexes with redox partners.

Amino Acid Sequence↗

PubMed1989

Crystallization of yeast iso-2-cytochrome c using a novel hair seeding technique.

A hair seeding technique has been developed to obtain diffraction quality crystals of yeast (Saccharomyces cerevisiae) iso-2-cytochrome c, a model for studies of protein folding and biological electron transfer reactions. Deep red crystals of this protein were obtained from 88 to 92% saturated solutions of ammonium sulfate containing 20 mg protein/ml, 0.1 M-sodium phoshate, 0.3 M-sodium chloride, 0.04 M-dithiothreitol and adjusted to phosphate, 0.3 M-sodium chloride, 0.04 M-dithiothreitol and adjusted to pH 6.0. Rapid crystal growth was observed, but only along the path of the seeding hair stroke. The space group is P4(3)2(1)2 (or P4(1)2(1)2) with a = b = 36.4 A, c = 137.8 A (1 A = 0.1 nm) and Z = 8. Crystals are stable in the X-ray beam for more than 10 days and diffract to at least 2.5 A resolution. The same hair seeding methodology has proven useful in obtaining crystals of specifically designed mutant iso-2 proteins and in other protein systems where consistent crystal growth had previously proven difficult to attain.

Crystallization↗

PubMed1989

A moderate form of hemophilia B is caused by a novel mutation in the protease domain of factor IXVancouver.

A genomic phage library was constructed using lymphocyte DNA from a patient with cross-reacting material-positive, moderately severe hemophilia B. The library was screened by using a full-length factor IX cDNA as a hybridization probe. DNA sequence analysis of the factor IX exons and intron/exon junctions revealed a single point mutation at nucleotide 31,311 of the gene. This mutation occurs in the protease domain of factor IXa and changes the codon for isoleucine 397 (ATA) to a threonine codon (ACA). The resulting abnormal protein has been named factor IXVancouver. Factor IXVancouver was isolated from the patient's plasma by barium citrate adsorption, affinity chromatography on a Ca2+-dependent antibody bound to agarose, and anion-exchange chromatography. On gel electrophoresis, the purified protein exhibited a normal molecular weight and a normal pattern of activation cleavages with bovine factor XIa. Kinetic studies on the purified protein indicated that the Km of factor IXaVancouver for human factor X was 3.4 times higher than that of normal factor IXa. The kcat of factor IXaVancouver was 12.5% of the kcat of normal factor IXa. Structural models of the protease domain of human factor IXa and of factor IXaVancouver were constructed, based on the homology of factor IXa with related serine proteases of known structure. The factor IXaVancouver model suggests that hydrogen bonding between the side chain hydroxyl group of threonine 397 and the carbonyl oxygen of tryptophan 385 reduces the ability of factor IXaVancouver to bind factor X in a configuration favoring catalysis.

Amino Acid Sequence↗

PubMed1989

Canine hemophilia B resulting from a point mutation with unusual consequences.

We have used the polymerase chain reaction to amplify the entire coding region of canine factor IX from a hemophilia B animal. When the sequence was compared to that which codes for normal canine factor IX, a single missense mutation was identified. This mutation (G----A at nucleotide 1477) results in the substitution of glutamic acid for glycine-379 in the catalytic domain of the molecule. The mutation creates a new restriction site that allowed confirmation of the abnormal sequence in both hemophilic and carrier animals. Amino acid 379 in canine factor IX corresponds to position 381 in human factor IX, a location at which no human mutations have been described. Moreover, it occurs at one of the few amino acids that have been rigorously conserved among the trypsin-like serine proteases throughout evolution. The mutation responsible for canine hemophilia B results in a complete lack of circulating factor IX in the affected animals. As it is unusual for a missense mutation to result in a complete absence of protein product, structural modeling of the mutant and normal proteins was pursued. These studies suggest that the observed mutation would have major adverse effects on the tertiary structure of the aberrant factor IX molecule. The elucidation of this mutation sheds light on structure-function relationships in factor IX and should facilitate future experiments directed toward gene therapy of this disease.

Amino Acid Sequence↗

PubMed1988

Role of phenylalanine-82 in yeast iso-1-cytochrome c and remote conformational changes induced by a serine residue at this position.

A three-dimensional structural analysis of the reduced form of the Ser-82 mutant protein of yeast iso-1-cytochrome c has been completed to 2.8-A resolution. Replacement of Phe-82 with a serine residue results in conformational changes both near and remote from the mutation site. Those groups undergoing positional shifts near Ser-82 include Arg-13, Gly-83 and -84, and the CBB methyl of the heme group. Remote shifts are centered about the propionate of pyrrole ring A and principally involve Asn-52, Trp-59, and an internally buried water molecule, WAT-166. Placement of a serine side chain at position 82 also leads to the formation of a large solvent channel which substantially increases the solvent accessibility of the heme group. This would appear to account for the much lower reduction potential observed for this protein. The detrimental effect of Ser-82 on both the steady-state activity and the rate of electron transfer in complexation with cytochrome c peroxidase can also be interpreted in terms of the modified character of the region about the mutation site. The remote conformational changes observed appear to represent the equivalent of the initial conformational changes occurring as yeast iso-1-cytochrome c is converted to the fully oxidized state during an electron-transfer event. These results agree well with the proposal [Moore, G. R. (1983) FEBS Lett. 161, 171-175] that the trigger for conformational changes between oxidation states resides in the nature of the interactions between the heme iron atom and the pyrrole ring A propionate group.

Cytochrome c Group↗

PubMed1988

Large-scale purification and biochemical characterization of crystallization-grade porin protein P from Pseudomonas aeruginosa.

A large-scale purification scheme was developed for lipopolysaccharide-free protein P, the phosphate-starvation-inducible outer-membrane porin from Pseudomonas aeruginosa. This highly purified protein P was used to successfully form hexagonal crystals in the presence of n-octyl-beta-glucopyranoside. Amino-acid analysis indicated that protein P had a similar composition to other bacterial outer membrane proteins, containing a high percentage (50%) of hydrophilic residues. The amino-terminal sequence of this protein, although not homologous to either outer membrane protein, PhoE or OmpF, of Escherichia coli, was found to have an analogous protein-folding pattern. Protein P in the native trimer form was capable of maintaining a stable functional trimer after proteinase cleavage. This suggested the existence of a strongly associated tertiary and quaternary structure. Circular dichroism studies confirmed these results in that a large proportion of the protein structure was determined to be beta-sheet and resistant to acid pH and heating in 0.1% sodium dodecyl sulphate.

Amino Acid Sequence↗

PubMed1988

Horse heart metmyoglobin. A 2.8-A resolution three-dimensional structure determination.

The structure of horse heart metmyoglobin has been determined with a molecular replacement approach and subsequently refined using rigid body and restrained-parameter least squares methods to a conventional crystallographic R-factor of 0.16 for all observed reflections in the 6.0-2.8-A resolution range. The polypeptide chain of this protein is found to be organized into eight helical regions (labeled A-H) which collectively form a hydrophobic pocket in which the heme prosthetic group is bound. Our results show that the overall thermal motions of individual residues of horse heart metmyoglobin are correlated with their mean distances from the heme group. In comparisons with the structure of sperm whale metmyoglobin it has been found that horse heart metmyoglobin has unique polypeptide chain conformations in four regions. These include residues in the immediate vicinity of the amino and carboxyl termini, residues about Lys-16, and residues 117-124 which are in the interhelical region between helices G and H. Many of these conformational changes appear to occur as a consequence of a different pattern of salt-bridging interactions between charged residues on the surface of horse heart metmyoglobin. The overall average positional deviation observed between corresponding alpha-carbons in the polypeptide chains of horse heart and sperm whale metmyoglobin is 0.50 A. This value for atoms of the porphyrin core of the central heme group is 0.39 A. A total of 12 well defined water molecules and 1 sulfate ion are included in the current structural model of horse heart metmyoglobin. One of these water molecules is found to be coordinated to the heme iron atom and hydrogen bonded to the side chain of His-64. The sulfate ion is hydrogen bonded to amide groups at the amino-terminal end of the E-helix and, as well, forms similar interactions with the amino-terminal end of the D-helix of an adjacent protein molecule in the crystalline lattice.

Animals↗

PubMed1988

Yeast iso-1-cytochrome c. A 2.8 A resolution three-dimensional structure determination.

A molecular replacement approach, augmented with the results of predictive modeling procedures, solvent accessibility studies, packing analyses and translational coefficient searches, has been used to elucidate the 2.8 A (1 A = 0.1 nm) resolution structure of yeast iso-1-cytochrome c. An examination of the polypeptide chain folding of this protein shows it to have unique conformations in three regions, upon comparison with the structures of other eukaryotic cytochromes c. These include: residues -5 to +1 at the N-terminal end of the polypeptide chain, which are in an extended conformation and project in large part off the surface of the protein; residues 19 to 26, which form a surface beta-loop on the His18 ligand side of the central heme group; and, the C-terminal end of the helical segment composed of residues 49 to 56, which serves to form a part of the heme pocket. Structural studies also show that the highly reactive sulfhydryl group of Cys102 is buried within a hydrophobic region in the monomer form of yeast iso-1-cytochrome c. Dimerization of yeast iso-1-cytochrome c through disulfide bond formation between two such residues would require a substantial conformational change in the C-terminal helix of this protein. Another unique structural feature, the trimethylated side-chain of Lys72, is located on the surface of yeast iso-1-cytochrome c near the solvent-exposed edge of the bound heme prosthetic group. On the basis of the results of these and other structural studies, an analysis of the spatial conservation of structural features in the heme pocket of eukaryotic cytochromes c has been conducted. It was found that the residues involved could be divided into three general classes. The current structural analyses and additional modeling studies have also been used to explain the altered functional properties observed for mutant yeast iso-1-cytochrome c proteins.

Amino Acid Sequence↗

PubMed1987

Crystallization and preliminary diffraction data for horse heart metmyoglobin.

Reddish-brown crystals of metmyoglobin from horse heart have been obtained by both the hanging drop and batch crystallization methods in the space group P2(1), having a = 64.3 A, b = 28.9 A and c = 35.9 A, with beta = 107.1 degree. Morphologically similar crystal forms have been obtained for three derivatives of horse heart myoglobin having modified heme prosthetic groups.

Animals↗

PubMed1987

A preliminary structure for the DNA binding protein from bacteriophage IKe.

A modelling procedure has been utilized to obtain a preliminary three-dimensional structural model for the bacteriophage IKe DNA binding protein (IKe-DBP) based on the known high resolution X-ray diffraction structure of a functionally related protein (G5BP) from bacteriophage fd. The degree of structural homology observed is much higher than the 44% primary sequence identity between these proteins would indicate. These studies suggest IKe-DBP, like G5BP, is composed of a central three-stranded beta sheet from which protrude three extended beta loops. Furthermore, the IKe-DBP structural model can easily form, without conformational rearrangements, the compact dimer unit that is the functionally active species of G5BP. Structural comparisons show residues conserved in the primary sequence of both proteins tend to cluster in two regions. The first being essential for the maintenance of dimer association. The second about the two DNA binding channels which cross the face of each dimer. Based upon an earlier characterized G5BP-DNA complex, a model for DNA complexation to IKe-DBP is also presented.

Amino Acid Sequence↗

PubMed1987

Structural basis for regulation in gram-negative bacterial citrate synthases.

The citrate synthases of Gram-negative bacteria, unlike those of eukaryotes, are inhibited allosterically by NADH, but the two kinds of citrate synthase are about 30% homologous in amino acid sequence--the two Gram-negative citrate synthase sequences so far determined, from Escherichia coli and Acinetobacter anitratum, are about 70% identical. A model for the NADH-sensitive E. coli citrate synthase has been constructed using sequence homology and the known structure of the pig heart enzyme. The most reactive cysteine in the E. coli enzyme, which probably marks the NADH binding site, has now been identified as Cys-206. The model places this residue far from the active site. An E. coli citrate synthase mutant, from which a stretch of 24 amino acids has been deleted near the active site, still binds NADH normally. Two active site missense mutants of this enzyme, generated by oligonucleotide-directed mutagenesis, have lower affinities for one substrate, oxaloacetate, but also are much less sensitive to 2-oxoglutarate, an oxaloacetate analogue hitherto believed to be an allosteric inhibitor. These results confirm that NADH binds to a truly allosteric site in E. coli citrate synthase, the features of which are still to be defined; while 2-oxoglutarate is really an active-site directed inhibitor, although it may still play a regulatory role in vivo.

Binding Sites↗

PubMed1986

Crystal structure of RNase A complexed with d(pA)4.

Co-crystals of pancreatic RNase A complexed with oligomers of d(pA)4 were grown from polyethylene glycol 4000 at low ionic strength and the X-ray diffraction data were collected to 2.5 A resolution. From a series of heavy-atom derivatives a multiple isomorphous replacement-phased electron density map of the RNase-d(pA)4 complex was calculated to 3.5 A. By inspection, the disposition of the known structure of RNase in the unit cell was determined and this was confirmed by calculation of a standard crystallographic residual, R. Refinement of the protein alone in the unit cell as a strictly rigid body yielded an R factor of 0.32 at 2.8 A resolution. From difference Fourier syntheses DNA fragments were elucidated and incorporated into a model of the complex. The entire asymmetric unit was refined using a restrained-constrained least-squares procedure (CORELS) interspersed with difference Fourier syntheses. At the present time the crystal structure has been refined to an overall R value of 0.215 at 2.5 A resolution. The asymmetric unit of the complex crystals contains four oligomers of d(pA)4 associated with each molecule of RNase. In addition, there may also be partially ordered fragments of DNA at low occupancy present in the unit cell, but these have not, at this time, been incorporated into the model. One tetramer of d(pA)4 is entirely bound by a single protein molecule and occupies a portion of the active site cleft, filling the purine binding site and the phosphate site at the catalytic center with its 5' nucleotide. Two other tetramers are partly intermolecular. One passes from near the pyrimidine binding site over the surface of the protein toward arginine 39 and into a solvent region. A third tetramer is anchored at its 5' terminus by a salt link to lysine 98, passes near arginine and then through a solvent region to terminate with its 3' end near the surface of another protein molecule in the lattice. The fourth tetramer of d(pA)4 is bound at its 5' end on the opposite side of the protein from the active site in an electropositive anion trap that includes lysines 31 and 91 as well as arginine 33. There may be a DNA-DNA interaction involving the 5' phosphate of one tetramer and the 3' bases of two other tetramers and this may help to stabilize the crystalline complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1986

A catalogue of phi, psi and omega torsion angles for tetrapeptides in proteins.

This work examined the degree of consistency, over multiple occurrences in several proteins, of conformations of tetrapeptides. A data base of 114 proteins was taken from the Brookhaven Data Bank. The number of occurrences of every tetrapeptide in these proteins was counted. For each tetrapeptide which occurred more than 6 times all phi, psi and omega angles were calculated and averaged over the occurrences. Due to the limitations of the data base there were only 24 tetrapeptides in this category. This does not provide sufficient information for the extensive prediction of structures which are not homologous to those already in the data base but the effectiveness of structure prediction can be expected to increase with the size of the data base.

Oligopeptides↗