X-ray crystallographic analyses of complexes between bovine β-trypsin and schiff base copper(II) or iron(III) chelates

Toyota, Eiji; Ng, Kenneth; Sekizaki, Horuo; Itoh, Ken; Tanizawa, Kazutaka; James, Michael N.G.

doi:10.1006/jmbi.2000.4303

Cited by 38 publications

(18 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Their NH1 atoms have replaced the OW1 molecule and the second carbon connected to NH1 occupies Position2, which is usually a cation-binding site. The results from Kurinov and Harrison thus show a highly unusual binding arrangement of an amine type of ligand to trypsin, and to our knowledge this has not been seen for any other trypsin inhibitor complexes, neither with proteinase inhibitors (Rühlmann et al 1973;Helland et al 1998Helland et al , 1999a nor with complexes with small molecules (Whitlow et al 1999;Maignan et al 2000;Toyota et al 2001). Our crystallization conditions are identical to those of Kurinov and Harrison, but nevertheless resulted in different space groups, P2 1 2 1 2 1 and P3 1 21, respectively.…”

Section: Overall Binding Patternsupporting

confidence: 57%

Trypsin specificity as elucidated by LIE calculations, X‐ray structures, and association constant measurements

et al. 2004

View full text Add to dashboard Cite

The variation in inhibitor specificity for five different amine inhibitors bound to CST, BT, and the coldadapted AST has been studied by use of association constant measurements, structural analysis of highresolution crystal structures, and the LIE method. Experimental data show that AST binds the 1BZA and 2BEA inhibitors 0.8 and 0.5 kcal/mole more strongly than BT. However, structural interactions and orientations of the inhibitors within the S1 site have been found to be virtually identical in the three enzymes studied. For example, the four water molecules in the inhibitor-free structures of AST and BT are channeled into similar positions in the S1 site, and the nitrogen atom(s) of the inhibitors are found in two cationic binding sites denoted Position1 and Position2. The hydrophobic binding contributions for all five inhibitors, estimated by the LIE calculations, are also in the same order (−2.1 ± 0.2 kcal/mole) for all three enzymes. Our hypothesis is therefore that the observed variation in inhibitor binding arises from different electrostatic interactions originating from residues outside the S1 site. This is well illustrated by AST, in which Asp 150 and Glu 221B, despite some distance from the S1 binding site, lower the electrostatic potential of the S1 site and thus enhance substrate binding. Because the trends in the experimentally determined binding energies were reproduced by the LIE calculations after adding the contribution from long-range interactions, we find this method very suitable for rational studies of protein-substrate interactions.

show abstract

Section: Overall Binding Patternsupporting

confidence: 57%

Trypsin specificity as elucidated by LIE calculations, X‐ray structures, and association constant measurements

et al. 2004

View full text Add to dashboard Cite

show abstract

“…As for the extent of the studies of copper(II) Schiff base complexes derived from salicylaldehyde and amino acids, the first extensive observations were performed in the 1950s when the vitamin B6-like activities were described. Since then, a wide screening of biological activity was carried out and the SOD-mimic [8][9][10][11][12], radioprotective [8], antibacterial [13][14][15][16], antimycotic [13], fungistatic [10,13], antirheumatic [17], antipyretic and antidiabetic [18,19] activities were discovered and interactions with different biomolecules were described [20][21][22][23][24][25][26][27][28][29]. In contrast to a high number of papers dedicated to the studies of copper(II) complexes with Schiff bases derived from salicylaldehyde and amino acids, there are only a few works studying the structure of zinc(II) complexes [30].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, structural characterization, antiradical and antidiabetic activities of copper(II) and zinc(II) Schiff base complexes derived from salicylaldehyde and β-alanine

Vančo

Marek

Trávníček

et al. 2008

Journal of Inorganic Biochemistry

161

View full text Add to dashboard Cite

“…Tanizawa et al designed Schiff base chelate complexes of Cu(II) and Fe(III) as inhibitors of the serine proteases trypsin and thrombin [15,16]. The Schiff base ligands were obtained by condensing 4-formyl-3-hydroxybenzamidines or 3-formyl-4-hydroxybenzamidines with amino acids.…”

Section: Metal Complexes As Structural Scaffoldsmentioning

confidence: 99%

Organometallics as Structural Scaffolds for Enzyme Inhibitor Design

Mulcahy

Meggers

2010

Topics in Organometallic Chemistry

View full text Add to dashboard Cite

Substitutionally inert metal-containing compounds provide new opportunities as structurally diverse and unique scaffolds for the design of protein binders. This review cites progress in this area by highlighting the use of metal complexes, including truly organometallic compounds, as inhibitors for enzymes of biological interest, such as esterases, proteases, and protein kinases. A common theme in all discussed examples is the use of the metal center as an anchor for the 3D display of organic ligands. While the metal center does not engage in any direct contacts to protein residues, it is the structural orientation of the ligands into previously unaccessible architectures that make metal complexes emerging candidates for bioactive agents with unique properties.

show abstract

X-ray crystallographic analyses of complexes between bovine β-trypsin and schiff base copper(II) or iron(III) chelates

Cited by 38 publications

References 27 publications

Trypsin specificity as elucidated by LIE calculations, X‐ray structures, and association constant measurements

Trypsin specificity as elucidated by LIE calculations, X‐ray structures, and association constant measurements

Synthesis, structural characterization, antiradical and antidiabetic activities of copper(II) and zinc(II) Schiff base complexes derived from salicylaldehyde and β-alanine

Organometallics as Structural Scaffolds for Enzyme Inhibitor Design

Contact Info

Product

Resources

About