Protein-inhibitor complexes

McPhalen, C. A., James, M. N. G. Structural comparison of two serine proteinase-protein inhibitor complexes Eglin-C-Subtilisin Carlsberg and CI-2-subtilisin novo. Biochemistry 27 (1988) 6582-6598... 

Bash P A, U C Singh, F K Brown, R Langridge and P A Kollman 1987. Calculation of the Relat Change in Binding Free-Energy of a Protein-Inhibitor Complex. Science 235 574-576. 

Bash, P. A. Singh, U. C. Brown, F. K. Langridge, R. Kollman, P. A., Calculation of the relative change in binding free energy of a protein-inhibitor complex, Science 1987, 235, 574-576... 

The development of high-resolution 3D structures of proteins or protein-inhibitor complexes, however, was crucial in rapidly developing medicinals, although more so in the optimization phase of lead structures than in the discovery phase. 

In this section, some of the approaches described above for enhancing the sensitivity and information content of protein-ligand NOEs are demonstrated for relatively large protein-inhibitor complexes. In addition, we demonstrate that a medium-quality 3D X-filtered NOESY spectrum can be obtained for a large protein-inhibitor complex by using a stabilized, uniformly 13C/15N-labeled protein sample in conjunction with an elevated experimental temperature to increase the rotational correlation time of the protein-ligand complex. 

SI Ft Analysis, Organization and Database Mining for Protein-Inhibitor Complexes. 

A structural interaction fingerprint is a ID binary representation of the interaction patterns from a 3D protein-inhibitor complex. The fingerprint representation of the interaction patterns is compact and allows for rapid clustering and analysis of massive numbers of complexes. 

STD-NMR cannot readily distinguish between specific and nonspecific binding events. Therefore, an extension of STD-NMR involves the titration of a protein-inhibitor complex with a test ligand that will compete with the inhibitor in fast exchange for the same receptor-binding site on the protein. This situation... 

The overall structure of these metalloproteins is characterized by a deep active site cleft that divides the molecule into two domains, with the catalytically active zinc located at the bottom of the active site in the center of the molecule (Fig. 3). The structures of protein-inhibitor complexes [15,17,19-26] representing different families, indicate that the PI residue [37] is the principal recognition element for these enzymes (Fig. 5). Inhibitors bound to members of the matrixin family [17,19-23,25] adopt an extended conformation (Fig. 6), with the side chain at the P2 subsite directed away from the enz5mie on the opposite side of the inhibitor backbone to the PI specificity pocket. In addition to the zinc ligands, there are essential enzyme-inhibitor interactions between backbone atoms of the protein and complementary atoms of the inhibitor 1. 

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