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H Umeyama

Publications and source records attributed to H Umeyama.

78 records · Page 5Linked to original sources
PubMedDate not supplied

Amino acid similarity matrix for homology modeling derived from structural alignment and optimized by the Monte Carlo method.

In this paper, we obtained a similarity matrix for homology modeling based on the structure of proteins in a structural alignment. The alignment procedure was executed within dynamic programming generally used in alignment methods. An initial matrix derived from the structural alignment was optimized by the Markov chain Monte Carlo method at low temperature to fit its sequence alignment to the structural alignment. Structural alignment was performed on the basis of the superposition of C alpha atoms for two protein structures. The objective function in the Monte Carlo procedure was defined by entropy in the information theory, allowing us to show that the amino acid similarity matrix aligned accurately. When compared with the structural alignment, the average number of incorrect amino acid residues in the sequence alignment was 22.6 for all residues and about 3.7 for residues in structurally conserved regions. The alignment with our matrix was more similar to structural alignment than to sequence alignments using other amino acid substitution matrices.

Algorithms↗
PubMedDate not supplied

Three-dimensional structure of human renin.

A three-dimensional model of human renin has been constructed based on the assumption that the overall folding of the aspartyl proteases is very similar. As a reference, we used penicillopepsin, the structure of which has been reported at a resolution of 1.8 A, and its main chain was traced to build a model of renin. The resulting structure seems to be stable from the hydrophobic and hydrophilic viewpoints. Comparison of the tertiary structure of human renin with that of penicillopepsin and mouse renin suggests the existence of a high structural homology as well as differences in the molecular geometry of the active sites that may influence the substrate specificity. The asparagine side chains in the glycosidation signal of Asn-X-Thr are exposed on the surface. Moreover, the site in human renin that corresponds to the proteolytic cleavage site in mouse renin also appears to be exposed on the surface so as to be easily scissored during the maturation process. The insertions and deletions of amino acid residues were found to arise on the surface, and in some places they occurred in complementary manners. Models of molecular complexes between human renin and renin inhibitor were constructed to understand the interacting modes that indicate how new renin inhibitors develop. Inhibitor-binding sites were directly assigned based on the models of the inhibitor-enzyme complex.

Amino Acid Sequence↗
PubMedDate not supplied

Design and synthesis of a kininogen-based selective inhibitor of thrombin-induced platelet aggregation.

Thrombin-induced platelet aggregation has been suggested to play an important role in reocclusion following thrombolytic therapy or angioplasty for treatment of myocardial infarction. We previously demonstrated that thrombin-induced platelet aggregation is indirectly mediated by intracellularly activated calpain expressed on the platelet surface through the cleavage of aggregin, a putative ADP-receptor, and that high molecular weight kininogen (HK), a naturally occurring thiol protease inhibitor, modulates thrombin-induced platelet aggregation. Considering the substrate specificity of calpain and the conserved sequence in HK, we studied selective inhibitors of thrombin-induced platelet aggregation by the affinity labeling approach with an S-3-nitro-2-pyridinesulfenyl (Npys) group. H-Phe-Gln-Val-Val-Cys (Npys)-Gly-NH2, which combines chemical and structural features of calpain substrate specificity and the conserved sequence in HK, selectively inhibited thrombin-induced platelet aggregation. It did not inhibit the aggregatory effects of other platelet agonists, and did not inhibit amidolytic activity of thrombin and thrombin-induced platelet shape change. The design and synthesis of such inhibitors could lead to the development of a new class of inhibitors that selectively block thrombin-induced platelet aggregation.

Amino Acid Sequence↗