Direct and reversed amino acid sequence pattern analysis: structural reasons for activity of reversed sequence sites and results of kinase site mutagenesis.
During studies of kinase phosphorylation, not all functional kinase phosphorylation may be found using consensus sequence patterns. This type of phosphorylation is termed 'non-consensus' or 'cryptic' phosphorylation. Results presented here based on molecular dynamics of short peptides show that protein kinases may phosphorylate not only established consensus sequences (reading a sequence from N-terminus to C-terminus) but also reversed consensus sequences (reading from C- to N-terminus). Several protein sequences were analysed and corresponding biochemical data were presented. Similarity of molecular shapes of direct and reversed consensus peptides, and sequence conservation in the regions of reversed sites in the analysed proteins, indicate that at least part of the phosphorylation sites considered as 'cryptic' may be explained in terms of reversed consensus pattern occurrences.
Torshin
I
I
Laboratory of Kinetic and Catalysis, Chemical Department, Moscow State University, Moscow, 119899, Russia. TIY@phys.chem.msu.ru
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000595:Amino Acid Sequence; D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins / Q000378:metabolism; D017124:Conserved Sequence; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D016296:Mutagenesis; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D010770:Phosphotransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide / Q000378:metabolism; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; C505032:CFTR protein, human; D002352:Carrier Proteins; D010455:Peptides; D018005:Receptors, Vasoactive Intestinal Peptide; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D010770:Phosphotransferases; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C