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P Argos

Publications and source records attributed to P Argos.

178 records · Page 10Linked to original sources
PubMed1977

Convergence of active center geometries.

Comparisons have been made between the active center geometries of lactate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase, chymotrypsin and papain, and glyceraldehyde-3-phosphate dehydrogenase and papain. In the dehydrogenases, orientation of the nicotinamide ring about the glycosidic bond is determined by the substrate stereochemistry. The proper positioning of the carboxyamide moiety allows for the close approach of the C4 atom on the nicotinamide and the reactive carbon of the substrate. It follows that, once the conformation of the substrate or substrate intermediate has been established with respect to the functional groups in the enzyme, the A- or B-side specificity of the nicotinamide ring is predetermined. Hence, dehydrogenases which are divergently evolving from a common precursor must maintain the nicotinamide specificity if the protein fold of the catalytic domain is conserved. The tetrahedral intermediates produced during acylation of chymotrypsin and papain are found to be of opposite hand, while those of papain and glyceraldehyde-3-phosphate dehydrogenase can be regarded to be of the same hand. Thus the serine proteases, subtilisin and those of the chymotrypsin family, are of one hand while the cysteine enzymes, glyceraldehyde-3-phosphate dehydrogenase and papain, are of the other.

Binding Sites↗
PubMed1977

Secondary-structure predictions of calcium-binding proteins.

The known tertiary structure of carp muscle parvalbumin is consistent with an "EF-hand" architecture (helix-loop-helix) for each calcium-ion binding site. Primary-sequence alignments have indicated four EF hands in rabbit skeletal muscle troponin C and in rabbit myosin alkali light chains. Five secondary-structure prediction methods, based on amino acid sequence only, have been fully computerized and used to calculate joint prediction histograms for several calcium-binding proteins. The joint histogram can suggest directly the extent and sequence of the helical- and loop-structural elements, as well as any secondary structural distortions or evolutionary developments. Since the histogram predicted well the length and sequence of secondary structural elements in carp muscle parvalbumin, it seemed reasonable to calculate the joint distribution for other proteins that might bind calcium through the EF-hand configuration. The histograms indicated the four EF-hand regions speculated fro rabbit skeletal muscle troponin C but suggested only three such hands in bovine cardiac muscle troponin C and with a distorted fourth hand. Considerable secondary structural distortion is postulated for the alkali light chains. Possible EF configurations consistent with the histogram results are speculated for Escherichia coli acyl-carrier protein and bovine prothrombin fragment 1, which have been shown to bind calcium. The secondary-structure-prediction algorithms appear to be a useful adjunct to sequence-alignment techniques, especially in cases where the primary sequence homology is weak or the evolutionary distance is large.

Amino Acid Sequence↗
PubMed1976

An assessment of protein secondary structure prediction methods based on amino acid sequence.

Five of the several secondary structure prediction methods based on protein amino acid sequence has been computerized, allowing the calculation of joint prediction histograms which have been shown to be superior to any individual prediction. The known structures of about 40 proteins experimentally determined by X-ray crystallography are compared with the predictions resulting from calculated histograms. The accuracy of the predictions for helices is generally much better than for both beta-sheet regions and for turns. The overall agreement between prediction and observation within the amino terminal half of the protein molecules is clearly superior to that for the carboxyl half, suggesting an amino nucleating core. Predictions for smaller proteins and thermally stable proteins are generally good, indicating the sensitivity of the methods to short-range but not long-range interactions. In less than half the cases tested were the predictions useful; there was no way of knowing ahead of time if a favorable prediction would result. Given the lack of dramatic improvement with an increase in data base for the schemes and the generally poor agreement factors, it appears that a perfect predictive algorithm must include a consideration of energy minimization, thermalization, and long-range interactions. Extreme caution is suggested in applying present prediction routines to unknown protein structures.

Amino Acid Sequence↗
PubMed1975

A comparison of the heme binding pocket in globins and cytochrome b5.

Of the 85 three-dimensionally characterized residues of cytochrome b5, 51 are found to be structurally and topologically equivalent to the globin fold. When these proteins have been superimposed, the heme irons are found to be less than 1.4 A separated and the heme normals are inclined by less than 9.5 degrees. The proximal histidine of the globins and two adjacent helices are equivalent to the sixth iron ligand and adjacent helices of cytochrome b5. Larger differences in structure are observed on the distal side of the heme, coincident with the most changeable part of the globin structures. The heme itself is rotated by 53 degrees about its normal but such a change is energetically minimal and conservative as the heme side groups are not directly involved in the function of the molecules. The beta-sheet of cytochrome b5 is inserted into a corresponding cavity of the globins forming an additional lining to the heme pocket. The roughly 50 residues missing at the carboxy end of the known cytochrome b5 fragment could correspond in part to the H helix in the globins. While it would seem probable that these similarities represent divergent evolution from a primordial heme-binding protein, the possibility of structural convergence to a functionally satisfactory protein cannot be excluded.

Amino Acid Sequence↗
PubMed1975

The structure of ferrocytochrome b5 at 2.8 A resolution.

Crystals of cytochrome b5 reduced by sodium dithionite are isomorphous with the oxidized form. An electron density difference map between the two forms was calculated at 2.8 A resolution. There are no changes in main chain conformation or internal side chain orientation upon reduction. However, an ion becomes attached at the entrance of the heme crevice causing displacement of a surface lysine side chain on an adjacent molecule. The ion, identified as a cation by the nature of its coordinating ligands, appears to neutralize one of the heme propionate groups which is partially buried. It is proposed that the negatively charged propionate serves to neutralize the net formal positive charge on the heme iron in the oxidized cytochrome and that the neutralization of the heme iron upon reduction then leads to binding of a cation to the propionate.

Animals↗
PubMedDate not supplied

Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A.

We have cloned and sequenced the complete complementary DNA of the oestrogen receptor (ER) present in the breast cancer cell line MCF-7. The expression of the ER cDNA in HeLa cells produces a protein that has the same relative molecular mass and binds oestradiol with the same affinity as the MCF-7 ER. There is extensive homology between the ER and the erb-A protein of the oncogenic avian erythroblastosis virus.

Amino Acid Sequence↗
PubMedDate not supplied

Fingers and helices.

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Amino Acid Sequence↗