References of "Fujihashi, Hirotomo"
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See detailResidues crucial for maintaining short paths in network communication mediate signaling in proteins
del Sol Mesa, Antonio UL; Fujihashi, Hirotomo; Amoros, Dolors et al

in Molecular Systems Biology (2009), 2

Here, we represent protein structures as residue interacting networks, which are assumed to involve a permanent flowof information between amino acids. By removal of nodes from the protein network, we ... [more ▼]

Here, we represent protein structures as residue interacting networks, which are assumed to involve a permanent flowof information between amino acids. By removal of nodes from the protein network, we identify fold centrally conserved residues, which are crucial for sustaining the shortest pathways and thus play key roles in long-range interactions. Analysis of seven protein families (myoglobins, G-protein-coupled receptors, the trypsin class of serine proteases, hemoglobins, oligosaccharide phosphorylases, nuclear receptor ligand-binding domains and retroviral proteases) confirms that experimentally many of these residues are important for allosteric communication. The agreement between the centrally conserved residues, which are key in preserving short path lengths, and residues experimentally suggested to mediate signaling further illustrates that topology plays an important role in network communication. Protein folds have evolved under constraints imposed by function. To maintain function, protein structures need to be robust to mutational events. On the other hand, robustness is accompanied by an extreme sensitivity at some crucial sites. Thus, here we propose that centrally conserved residues, whose removal increases the characteristic path length in protein networks, may relate to the system fragility. [less ▲]

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See detailResidue centrality, functionally important residues, and active site shape: analysis of enzyme and non-enzyme families.
del Sol Mesa, Antonio UL; Fujihashi, Hirotomo; Amoros, Dolors et al

in Protein science : a publication of the Protein Society (2006), 15(9), 2120-8

The representation of protein structures as small-world networks facilitates the search for topological determinants, which may relate to functionally important residues. Here, we aimed to investigate the ... [more ▼]

The representation of protein structures as small-world networks facilitates the search for topological determinants, which may relate to functionally important residues. Here, we aimed to investigate the performance of residue centrality, viewed as a family fold characteristic, in identifying functionally important residues in protein families. Our study is based on 46 families, including 29 enzyme and 17 non-enzyme families. A total of 80% of these central positions corresponded to active site residues or residues in direct contact with these sites. For enzyme families, this percentage increased to 91%, while for non-enzyme families the percentage decreased substantially to 48%. A total of 70% of these central positions are located in catalytic sites in the enzyme families, 64% are in hetero-atom binding sites in those families binding hetero-atoms, and only 16% belong to protein-protein interfaces in families with protein-protein interaction data. These differences reflect the active site shape: enzyme active sites locate in surface clefts, hetero-atom binding residues are in deep cavities, while protein-protein interactions involve a more planar configuration. On the other hand, not all surface cavities or clefts are comprised of central residues. Thus, closeness centrality identifies functionally important residues in enzymes. While here we focus on binding sites, we expect to identify key residues for the integration and transmission of the information to the rest of the protein, reflecting the relationship between fold and function. Residue centrality is more conserved than the protein sequence, emphasizing the robustness of protein structures. [less ▲]

Detailed reference viewed: 114 (0 UL)
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See detailResidues crucial for maintaining short paths in network communication mediate signaling in proteins.
del Sol Mesa, Antonio UL; Fujihashi, Hirotomo; Amoros, Dolors et al

in Molecular systems biology (2006), 2

Here, we represent protein structures as residue interacting networks, which are assumed to involve a permanent flow of information between amino acids. By removal of nodes from the protein network, we ... [more ▼]

Here, we represent protein structures as residue interacting networks, which are assumed to involve a permanent flow of information between amino acids. By removal of nodes from the protein network, we identify fold centrally conserved residues, which are crucial for sustaining the shortest pathways and thus play key roles in long-range interactions. Analysis of seven protein families (myoglobins, G-protein-coupled receptors, the trypsin class of serine proteases, hemoglobins, oligosaccharide phosphorylases, nuclear receptor ligand-binding domains and retroviral proteases) confirms that experimentally many of these residues are important for allosteric communication. The agreement between the centrally conserved residues, which are key in preserving short path lengths, and residues experimentally suggested to mediate signaling further illustrates that topology plays an important role in network communication. Protein folds have evolved under constraints imposed by function. To maintain function, protein structures need to be robust to mutational events. On the other hand, robustness is accompanied by an extreme sensitivity at some crucial sites. Thus, here we propose that centrally conserved residues, whose removal increases the characteristic path length in protein networks, may relate to the system fragility. [less ▲]

Detailed reference viewed: 95 (1 UL)
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See detailTopology of small-world networks of protein-protein complex structures.
del Sol Mesa, Antonio UL; Fujihashi, Hirotomo; O'Meara, Paul

in Bioinformatics (Oxford, England) (2005), 21(8), 1311-5

The majority of real examples of small-world networks exhibit a power law distribution of edges among the nodes, therefore not fitting into the wiring model proposed by Watts and Strogatz. However ... [more ▼]

The majority of real examples of small-world networks exhibit a power law distribution of edges among the nodes, therefore not fitting into the wiring model proposed by Watts and Strogatz. However, protein structures can be modeled as small-world networks, with a distribution of the number of links decaying exponentially as in the case of this wiring model. We approach the protein-protein interaction mechanism by viewing it as a particular rewiring occurring in the system of two small-world networks represented by the monomers, where a re-arrangement of links takes place upon dimerization leaving the small-world character in the dimer network. Due to this rewiring, the most central residues at the complex interfaces tend to form clusters, which are not homogenously distributed. We show that these highly central residues are strongly correlated with the presence of hot spots of binding free energy. CONTACT: ao-mesa@fujirebio.co.jp SUPPLEMENTARY INFORMATION: http://www.fujirebio.co.jp/support/index.php (under construction). [less ▲]

Detailed reference viewed: 133 (1 UL)