title: Solution structure of cysteine-rich domain of protein kinase C alpha.
abstract: The three-dimensional structure of the second cysteine-rich domain of protein kinase C alpha (residues 95-159) was determined in aqueous solution by two-dimensional proton nuclear magnetic resonance and simulated annealing based calculations. On the basis of 687 distance constraints derived from assigned nuclear Overhauser effect (NOE) connectivities, a total of 10 converged structures were obtained from 40 runs of calculations. The atomic root-mean-square (RMS) difference about the mean coordinate positions (excluding residues 1-7, 16-17, 30-34, and 55-65) is 0.55 A for backbone atoms (N, C alpha, C') and 1.07 A for all non-hydrogen atoms. The molecular scaffold is maintained by triple-stranded and double-stranded twisted beta-sheets packed against an alpha-helix and two independent zincs are coordinated by His8, Cys38, Cys41, Cys57 and Cys21, Cys24, His46, Cys49, respectively. It should be noted that the metal ligands from the two sites are interleaved and this is thought to be a new structural motif of a zinc finger domain. Based on the resultant structure, we propose an interaction site of the cysteine-rich domain of protein kinase C with diacylglycerols and phorbol esters.
authors.affiliation: Department of Molecular Physiology, The Tokyo Metropolitan Institute of Medical Science.
authors.forename: S
authors.initials: S
authors.lastname: Ichikawa
authors.forename: H
authors.initials: H
authors.lastname: Hatanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: S
authors.initials: S
authors.lastname: Ohno
authors.forename: F
authors.initials: F
authors.lastname: Inagaki
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D003545:Cysteine / Q000032:analysis*; D004075:Diglycerides / Q000378:metabolism; D007527:Isoenzymes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000737:chemistry*; D051571:Protein Kinase C-alpha; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012996:Solutions; D015032:Zinc / Q000378:metabolism
chemical_list: D004075:Diglycerides; D007527:Isoenzymes; D012996:Solutions; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D015032:Zinc; D003545:Cysteine