Aromatic side‐chain interactions in proteins. II. Near‐ and far‐sequence Phe‐X pairs

We have collected all aromatic pairs (3152) involving an N‐phenyl partner in a dataset of 593 proteins of the PDB: 728 of these pairs involve a partner residue less than 6 apart in the sequence. These near‐sequence Phe‐X pairs correspond to specific conformations that stabilize secondary structures, mainly α‐helices when the residues are 1, 3, and 4 apart, and β‐strands when they are 2 apart in the sequence. These conformations are not spatially random and have been examined in detail. The remaining phenylalanine pairs (2424) are between partners more than 5 apart in the sequence. Of these far‐sequence pairs, 34% of occurrences are in sheets. Next in frequencies are pairs that bridge a β‐strand to a helix (24%), followed by pairs that bridge a β‐strand to a random coiled structure (15%). Helix to helix pairs only constitute 12% of these far‐sequence pairs. Analysis of the pairing frequency supports the hypothesis that aromatic interactions are late events of protein folding. Proteins 2002;48:635–644. © 2002 Wiley‐Liss, Inc.

[1]  M. Nishio,et al.  CH/pi interactions as demonstrated in the crystal structure of guanine-nucleotide binding proteins, Src homology-2 domains and human growth hormone in complex with their specific ligands. , 1998, Bioorganic & medicinal chemistry.

[2]  A. Alonso,et al.  Protein tyrosine phosphorylation in T cell signaling. , 2002, Frontiers in bioscience : a journal and virtual library.

[3]  N. Kannan,et al.  Aromatic clusters: a determinant of thermal stability of thermophilic proteins. , 2000, Protein engineering.

[4]  R. Cummings,et al.  N-terminal residues in murine P-selectin glycoprotein ligand-1 required for binding to murine P-selectin. , 2003, Blood.

[5]  S. Akman,et al.  Formation of DNA-protein cross-links in cultured mammalian cells upon treatment with iron ions. , 1995, Free radical biology & medicine.

[6]  N. Green,et al.  The crystal structure of an aldehyde reductase Y50F mutant-NADP complex and its implications for substrate binding. , 2001, Chemico-biological interactions.

[7]  T. Kohzuma,et al.  The Structure and Unusual pH Dependence of Plastocyanin from the Fern Dryopteris crassirhizoma , 1999, The Journal of Biological Chemistry.

[8]  Francesco Luigi Gervasio,et al.  The nature of intermolecular interactions between aromatic amino acid residues , 2002, Proteins.

[9]  E. Pérez-Payá,et al.  Thermal stabilization of the catalytic domain of botulinum neurotoxin E by phosphorylation of a single tyrosine residue. , 2001, Biochemistry.

[10]  B. Charloteaux,et al.  Aromatic side‐chain interactions in proteins. I. Main structural features , 2002, Proteins.

[11]  B. Mannervik,et al.  A highly acidic tyrosine 9 and a normally titrating tyrosine 212 contribute to the catalytic mechanism of human glutathione transferase A4-4. , 2001, Biochemical and biophysical research communications.

[12]  M. Beinfeld.  Biosynthesis and processing of pro CCK: recent progress and future challenges. , 2003, Life sciences.

[13]  M. Cadene,et al.  Tyrosine sulfation of CCR5 N-terminal peptide by tyrosylprotein sulfotransferases 1 and 2 follows a discrete pattern and temporal sequence , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[14]  R. Srinivasan,et al.  LINUS: A hierarchic procedure to predict the fold of a protein , 1995, Proteins.

[15]  E. Haggård-Ljungquist,et al.  The two active-site tyrosine residues of the a protein play non-equivalent roles during initiation of rolling circle replication of bacteriophage p2. , 2001, Journal of molecular biology.

[16]  R. L. Baldwin,et al.  Side‐chain interactions in the C‐peptide helix: Phe 8 ⃛ His 12+ , 1990, Biopolymers.

[17]  S. Hubbard,et al.  Protein tyrosine kinase structure and function. , 2000, Annual review of biochemistry.

[18]  A. Pingoud,et al.  Involvement of conserved histidine, lysine and tyrosine residues in the mechanism of DNA cleavage by the caspase-3 activated DNase CAD. , 2002, Nucleic acids research.

[19]  F A Quiocho,et al.  mRNA cap recognition: dominant role of enhanced stacking interactions between methylated bases and protein aromatic side chains. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[20]  A. Shrake,et al.  Environment and exposure to solvent of protein atoms. Lysozyme and insulin. , 1973, Journal of molecular biology.

[21]  C. Bertozzi,et al.  Tyrosine sulfation: a modulator of extracellular protein-protein interactions. , 2000, Chemistry & biology.

[22]  K. Vrana,et al.  Identification of substrate orienting and phosphorylation sites within tryptophan hydroxylase using homology-based molecular modeling. , 2000, Journal of molecular biology.

[23]  C. Füll.  Bicyclic triterpenes as new main products of squalene–hopene cyclase by mutation at conserved tyrosine residues , 2001, FEBS letters.

[24]  J. Kopeček,et al.  Photodynamic Crosslinking of Proteins. III. Kinetics of the FMN‐ and Rose Bengal‐sensitized Photooxidation and Intermolecular Crosslinking of Model Tyrosine‐containing N‐(2‐Hydroxypropyl)methacrylamide Copolymers , 1999, Photochemistry and photobiology.

[25]  Hemalatha Balaram,et al.  Subunit interface mutation disrupting an aromatic cluster in Plasmodium falciparum triosephosphate isomerase: effect on dimer stability. , 2002, Protein engineering.

[26]  M. Nishio,et al.  CH/pi interactions in the crystal structure of TATA-box binding protein/DNA complexes. , 2000, Bioorganic & medicinal chemistry.

[27]  Juan Fernández-Recio,et al.  The Tryptophan/Histidine interaction in α-helices , 1997 .

[28]  S. Burley,et al.  Investigation of the Roles of Catalytic Residues in SerotoninN-Acetyltransferase* , 2002, The Journal of Biological Chemistry.

[29]  L. D. Ward,et al.  Roles of histidine 31 and tryptophan 34 in the structure, self-association, and folding of murine interleukin-6. , 1997, Biochemistry.

[30]  L Serrano,et al.  Aromatic-aromatic interactions and protein stability. Investigation by double-mutant cycles. , 1991, Journal of molecular biology.

[31]  E. Purisima,et al.  Contribution to activity of histidine-aromatic, amide-aromatic, and aromatic-aromatic interactions in the extended catalytic site of cysteine proteinases. , 1996, Biochemistry.

[32]  D. E. Anderson,et al.  Hydrophobic core repacking and aromatic–aromatic interaction in the thermostable mutant of T4 lysozyme ser 117 → phe , 1993, Protein science : a publication of the Protein Society.

[33]  Janet M. Thornton,et al.  The interaction between phenylalanine rings in proteins , 1985 .

[34]  U. Samanta,et al.  Environment of tryptophan side chains in proteins , 2000, Proteins.

[35]  J M Thornton,et al.  Pi-pi interactions: the geometry and energetics of phenylalanine-phenylalanine interactions in proteins. , 1991, Journal of molecular biology.

[36]  Structure based hyperthermostability of archaeal histone HPhA from Pyrococcus horikoshii. , 2003, Journal of molecular biology.

[37]  G A Petsko,et al.  Aromatic-aromatic interaction: a mechanism of protein structure stabilization. , 1985, Science.

[38]  C. Aston,et al.  Reduced Body Weight and Increased Postimplantation Fetal Death in Tyrosylprotein Sulfotransferase-1-deficient Mice* , 2002, The Journal of Biological Chemistry.

[39]  Margarita Salas,et al.  Phi29 DNA polymerase residues Tyr59, His61 and Phe69 of the highly conserved ExoII motif are essential for interaction with the terminal protein. , 2002, Nucleic acids research.

[40]  R. L. Baldwin,et al.  The (i,i+4) Phe-His Interaction Studied in an Alanine-based α-Helix , 1993 .

[41]  K. Chou,et al.  Prediction of protein secondary structure content. , 1999, Protein engineering.

[42]  A. Fersht,et al.  Histidine-aromatic interactions in barnase. Elevation of histidine pKa and contribution to protein stability. , 1992, Journal of molecular biology.

[43]  M. Brigitte,et al.  Dityrosine formation is impaired by tyrosine phosphorylation. , 1992, Biochemical and biophysical research communications.

[44]  M. Yaffe.  Phosphotyrosine-binding domains in signal transduction , 2002, Nature Reviews Molecular Cell Biology.

[45]  A. Alonso,et al.  Protein tyrosine phosphatases. , 2002, Frontiers in bioscience : a journal and virtual library.

[46]  B. Chong,et al.  Site-directed mutagenesis of platelet glycoprotein Ib alpha demonstrating residues involved in the sulfation of tyrosines 276, 278, and 279. , 2002, Blood.

[47]  Zhon-Yin Zhang,et al.  Protein tyrosine phosphatases: structure and function, substrate specificity, and inhibitor development. , 2002, Annual review of pharmacology and toxicology.

[48]  Z. Zhang,et al.  Protein tyrosine phosphatases: prospects for therapeutics. , 2001, Current opinion in chemical biology.

[49]  A. Jasanoff,et al.  Aromatic-histidine interactions in the zinc finger motif: structural inequivalence of phenylalanine and tyrosine in the hydrophobic core. , 1993, Biochemistry.

[50]  A. Burlingame,et al.  Novel inter‐protein cross‐link identified in the GGH‐ecotin D137Y dimer , 2001, Protein science : a publication of the Protein Society.

[51]  Identification and role of ionizing functional groups at the active center of Rhodotorula gracilis D‐amino acid oxidase , 2001, FEBS letters.

[52]  Annick Thomas,et al.  Pex, analytical tools for PDB files. I. GF‐Pex: Basic file to describe a protein , 2001, Proteins.

[53]  P A Frey,et al.  Mechanistic roles of Thr134, Tyr160, and Lys 164 in the reaction catalyzed by dTDP-glucose 4,6-dehydratase. , 2001, Biochemistry.

[54]  G. McGaughey,et al.  pi-Stacking interactions. Alive and well in proteins. , 1998, The Journal of biological chemistry.