Differential geometry and protein conformation. V. Medium‐range conformational influence of the individual amino acids

Abstract

SynopsisA previous differential geometric analysis of the conformational properties of the various amino acids has been extended to study their influence on folding over a larger backbone interval. In addition, statistical effects associated with variation in the number of the individual amino acids in the database have been treated in greater detail, using a simulation method. It is found that the amino acids can be divided into three groups on the basis of their conformational influence over four-C" units in the interval i -6 < j s i + 6. Group Ia is composed of .seven amino acids (His, Leu, Ala, Met, Lys, Gln, Ile) that encourage the formation of AR-helical structure. Group Ib (Glu, Phe, Trp, Val, Asp) is composed of amino acids with some helix-forming tendency but that also show positive extended-strand formation tendency. They therefore act BS a bridge between group Ia and group I1 (Cys, Gly, Asn, Pro, Arg, Ser, Thr, Tyr) that contains amino acids that encourage the formation of extended structure and bends. The detailed four-C" con formational properties of each of the amino acids are shown, and the ability of amino acids to exert conformational influence in both directions along the backbone is examined. It is shown that, in general, such influence extends farther in the N-terminal direction than in the C-terminal direction. A framework is briefly sketched for using the present data to investigate actual folding mechanisms.

Pseudotorsional OCCO backbone angle as a single descriptor of protein secondary structure

“…These considerations justify exploration of alternative descriptors of protein geometry, such as various pseudotorsional and pseudobond backbone angles (Levitt, 1976;Rackovsky & Goldstein, 1987;Rackovsky, 1990;Oldfield & Hubbard, 1994). In this paper, we have concentrated on one such descriptor, the pseudotorsional backbone OCCO angle (Fig.…”

“…Although the 4 and $ angle values assigned to each residue in a protein chain explicitly describe the conformation of the main chain, there have been several attempts to find simpler ways of describing protein conformations. Quite often the pseudobond and pseudotorsional angles formed by consecutive three and four backbone Ca atoms, respectively, were considered (Levitt, 1976;Rackovsky & Goldstein, 1987;Rackovsky, 1990;Oldfield & Hubbard, 1994). These attempts were initially motivated by the fact that many earlier determinations of protein tertiary structure by X-ray crystallography were limited to finding the C a atom coordinates only (e.g., Hubbard & Blundell, 1987).…”

Mutation of cysteine-88 in the Saccharomyces cerevisiae RAD6 protein abolishes its ubiquitin-conjugating activity and its various biological functions.

“…To determine whether Cys-88 in the RAD6 protein is the acceptor site for ubiquitin, we altered this residue by oligonucleotide-directed mutagenesis; alanine and valine were chosen to replace Cys-88 because they bear the most resemblance to cysteine in their effect on protein conformation (27). In immunoblotting experiments and during protein purification, we found that both rad6 Ala-88 and rad6 Val-88 produce a stable protein with an electrophoretic mobility and chromato- Formerly, we reported studies with the rad6-149 allele, which codes for a protein lacking the entire carboxyl-terminal polyacidic tail of wild-type RAD6 (9,14).…”

“…The RAD6-encoded protein (8) possesses a sole cysteine, corresponding to the 88th residue. To inactivate the E2 function of RAD6, we altered Cys-88 to alanine and valine, as these changes are least likely to disrupt the conformation of the protein (27).…”

Efficient Identification and Analysis of Substructures in Proteins Using the Kappa-Tau Framework: Left Turns and Helix c-cap Motifs

“…We will here show how to apply this approach for the purpose of extracting and analyzing substructures. A previously introduced differential geometric description of proteins by Rackovsky, Scheraga, and Goldstein (10,11,12,13,14,15,16) is mathematically completely different, not suitable for our purposes, and will not be followed here. The interested reader may consult the original references and our comments in I. essentially two measures of structural relatedness available and routinely used in such comparisons presently.…”