The structures of interleukin-1ß, basic fibroblastgrowth factor and Erythrina trypsin inhibitor have been analysedin order to determine whether the hydrophobic core remains conserved,even when the structures have extremely low sequence similarities.We find that there are significant differences in the way eachprotein achieves a satisfactory arrangement of core residuesand that positions which contribute to the core of one structureare not guaranteed to contribute to the integrity of another.Furthermore, the side-chain packing arrangements of these coreresidues vary significantly between the three structures. Duringthis analysis the side-chain rotamers for three independentlydetermined interleukin-1ß structures were also compared.It was found that although buried residues are generally inagreement the remaining residues frequently occupy differentrotamers in the three structures. This suggests that althoughmeaningful studies are possible for buried side-chains the resultsobtained from equivalent analyses of accessible residues shouldbe treated with caution. These results are discussed with specificreference to the optimization of side-chain packing in proteinsof known structure. 相似文献
A three-dimensional structure for human cytochrome P450IA1 waspredicted based on the crystal coordinates of cytochrome P450camfrom Pseudomonas putida. As there was only 15% residue identitybetween the two enzymes, additional information was used toestablish an accurate sequence alignment that is a prerequisitefor model building. Twelve representative eukaryotic sequenceswere aligned and a net prediction of secondary structure wasmatched against the known -helices and ß-sheets ofP450cam. The cam secondary structure provided a fixed main-chainframework onto which loops of appropriate length from the humanP450IA1 structure were added. The model-built structure of thehuman cytochrome conformed to the requirements for the segregationof polar and nonpolar residues between the core and the surface.The first 44 residues of human cytochrome P450 could not bebuilt into the model and sequence analysis suggested that residues126 formed a single membrane-spanning segment. Examinationof the sequences of cytochrome P450s from distinct gene familiessuggested specific residues that could account for the differencesin substrate specificity. A major substrate for P450IA1, 3-methyl-cholanthrene,was fitted into the proposed active site and this planar aromaticmolecule could be accommodated into the available cavity. Residuesthat are likely to interact with the haem were identified. Thesequence similarity between 59 eukaryotic enzymes was representedas a dendrogram that in general clustered according to genefamily. Until a crystallographic structure is available, thismodel-building study identifies potential residues in cytochromeP450s important in the function of these enzymes and these residuesare candidates for site-directed mutagenesis. 相似文献
The configurational sequences of 1,2-unit in a series of hydrogenated syndiotactic 1,2-polybutadienes were determined in relation to the sequence distribution of 1,2- and 1,4-units on the basis of the 13C-n.m.r. signal assignment of the methyl carbons. The observed triad distributions of 1,2- and 1,4-units and configurational distributions of the 1,2-unit are in good agreement with the calculated distributions from transition probabilities. The number average sequence lengths of the 1,2-unit and the 1,2-unit in the racemic addition are 5.7 to 8.0 and 4.1 to 5.4, respectively. From the extrapolation of the plot of the number average sequence length against the crystallinity of the starting 1,2-polybutadienes, the minimum sequence length for crystallization is estimated to be 3.7 for the 1,2-unit in the racemic addition. 相似文献