Disulfide bond plasticity in epidermal growth factor

• Published in: Proteins, structure, function, and bioinformatics Vol. 40; no. 1; pp. 168 - 174
• Main Authors: Sampoli Benitez, Benedetta A., Komives, Elizabeth A.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.07.2000
• Subjects: Animals; Computer Simulation; cysteine disulfide isomer; Disulfides - chemistry; Epidermal Growth Factor - chemistry; Isomerism; Mice; Models, Molecular; NMR solution structure; Protein Structure, Tertiary
• ISSN: 0887-3585; 1097-0134
• DOI: 10.1002/(SICI)1097-0134(20000701)40:1<168::AID-PROT180>3.0.CO;2-N

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.