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Disulfide bond plasticity in epidermal growth factor
Author(s) -
Sampoli Benitez Benedetta A.,
Komives Elizabeth A.
Publication year - 2000
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(20000701)40:1<168::aid-prot180>3.0.co;2-n
Subject(s) - dihedral angle , disulfide bond , epidermal growth factor , cysteine , chemistry , structural motif , crystallography , bioinformatics , stereochemistry , hydrogen bond , molecule , biochemistry , biology , receptor , enzyme , organic chemistry
Epidermal growth factor (EGF) has a (1‐3,2‐4,5‐6) disulfide‐bonding pattern. This pattern is found in nearly all EGF‐like domains, despite wide variation in sequences. Biological data from EGF and at least one EGF‐like domain show that disulfide bond isomers have significant bioactivity and suggests that the EGF fold can accommodate alternate disulfide‐bonding patterns. The disulfide bonds in murine EGF were altered to seven different patterns and structures were calculated incorporating all the restraints from the highest resolution restraint set available (Tejero et al., 1996). Results showed that besides the native (1‐3,2‐4,5‐6), two other disulfide‐bonding patterns: (1‐2,3‐4,5‐6) and (1‐3,2‐5,4‐6) satisfied the restraints as well as the native. The results for these two patterns were indistinguishable from the native on the basis of distance and dihedral violations, XPLOR energies, Procheck statistics, and RMSDs of the final set of structures. Two other disulfide bond patterns, (1‐2,3‐5, 4‐6) and (1‐4,2‐3,5‐6) were able to satisfy all the distance restraints but had one or more cysteine dihedral violations. For all seven isomers, the final calculated structures were highly similar to EGF with all‐atom RMSD's in the 1.5–2 Å range. These results suggest that the EGF backbone fold has the unique property of accommodating several different disulfide‐bonding patterns. Proteins 2000;40:168–174. © 2000 Wiley‐Liss, Inc.