Premium
Geometric preferences of crosslinked protein‐derived cofactors reveal a high propensity for near‐sequence pairs
Author(s) -
Swain Marla D.,
Benson David E.
Publication year - 2005
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/prot.20403
Subject(s) - cofactor , amino acid , cysteine , covalent bond , sequence (biology) , crystallography , peptide sequence , chemistry , side chain , metal , stereochemistry , protein structure , oxidizing agent , biochemistry , organic chemistry , enzyme , gene , polymer
Protein‐derived cofactors that are composed of covalently crosslinked amino acid side chains are of increasing importance in protein science. These crosslinked protein‐derived cofactors (CPDC) are formed either through direct oxidation by metal/O 2 ‐derived intermediates or through outer sphere oxidation by highly oxidizing cofactors. CPDCs that are formed by outer sphere oxidation do not require side‐chain precursors to be coordinated by a metal center, and therefore are more difficult to identify than those formed by direct oxidation. To better understand the propensity for CPDC formation by outer sphere oxidation, the geometrical preferences of CPDCs were examined. The Dezymer algorithm has been used to identify all putative CPDC‐forming mutations in 500 proteins. Geometrically, although chemically unrelated, these CPDCs were found to be similar to disulfide‐bonded cysteine pairs. Additionally, the percentage of near‐sequence pairs ( i and i +1 to i and i + 5) increased as the average C α ‐C α distance between the amino acid pairs increased. This survey also examined the protein databank for proteins with pre‐attack conformations for CPDCs, using non‐bonded contacts reported by Procheck. A total of 323 unique proteins was identified, with 55 being near‐sequence amino acid pairs. The high geometric propensity of near‐sequence amino acid pairs for forming CPDCs is significant due to difficulties associated with detection by structural or mass spectrometric methods. Proteins 2005. © 2005 Wiley‐Liss, Inc.