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Biological Catalysts (biological + catalyst)
Selected AbstractsEngineering Allosteric Regulation into Biological CatalystsCHEMBIOCHEM, Issue 18 2009Jacques Fastrez Prof. Abstract Enzymes and ribozymes constitute two classes of biological catalysts. The activity of many natural enzymes is regulated by the binding of ligands that have different structures than their substrates; these ligands are consequently called allosteric effectors. In most allosteric enzymes, the allosteric binding site lies far away from the active site. This implies that communication pathways must exist between these sites. While mechanisms of allosteric regulation were developed more than forty years ago, they continue to be revisited regularly. The improved understanding of these mechanisms has led in the past two decades to projects to transform several unregulated enzymes into allosterically regulated ones either by rational design or directed evolution techniques. More recently, ribozymes have also been the object of similar successful engineering efforts. In this review, after briefly summarising recent progress in the theories of allosteric regulation, several strategies to engineer allosteric regulations in enzymes and ribozymes are described and compared. These redesigned biological catalysts find applications in a variety of areas. [source] Theoretical Study of Catalytic Efficiency of a Diels,Alderase Catalytic Antibody: An Indirect Effect Produced During the Maturation ProcessCHEMISTRY - A EUROPEAN JOURNAL, Issue 2 2008Sergio Martí Dr. Abstract The Diels,Alder reaction is one of the most important and versatile transformations available to organic chemists for the construction of complex natural products, therapeutics agents, and synthetic materials. Given the lack of efficient enzymes capable of catalyzing this kind of reaction, it is of interest to ask whether a biological catalyst could be designed from an antibody-combining site. In the present work, a theoretical study of the different behavior of a germline catalytic antibody (CA) and its matured form, 39,A-11, that catalyze a Diels,Alder reaction has been carried out. A free-energy perturbation technique based on a hybrid quantum-mechanics/molecular-mechanics scheme, together with internal energy minimizations, has allowed free-energy profiles to be obtained for both CAs. The profiles show a smaller barrier for the matured form, which is in agreement with the experimental observation. Free-energy profiles were obtained with this methodology, thereby avoiding the much more demanding two-dimensional calculations of the energy surfaces that are normally required to study this kind of reaction. Structural analysis and energy evaluations of substrate,protein interactions have been performed from averaged structures, which allows understanding of how the single mutations carried out during the maturation process can be responsible for the observed fourfold enhancement of the catalytic rate constant. The conclusion is that the mutation effect in this studied germline CA produces a complex indirect effect through coupled movements of the backbone of the protein and the substrate. [source] Activation Function of Chloroperoxidase in the Presence of Metal Ions at Elevated Temperature from 25 to 55°CCHINESE JOURNAL OF CHEMISTRY, Issue 7 2009Qiang GAO Abstract The investigation and comparison of chlorination activity of chloroperoxidase (CPO) from Caldariomyces fumago in metal ion solutions to those in pure buffer indicated that CPO could be effectively activated by some alkaline-earth metals and transition metals. The obtained maximum relative activity of CPO was 1.33 time at 75 µmol·L,1 Ca2+, 1.37 time at 90 µmol·L,1 Mg2+, 1.34 time at 90 µmol·L,1 Ni2+, and 1.27 time at 105 µmol·L,1 Co2+ at 25°C. Moreover, the CPO stability against temperature was improved in the presence of the above metal ions. At 55°C, CPO could retain only about 40% of activity whereas 75% and 81% of activity were maintained in Mg2+ and Ca2+ media, respectively. It was suggested that the metal ions bind to the acid-base catalytic groups Glu183, His105 and Asp106 around the active site of CPO, and activate CPO by both an enrichment of substrate concentration and the conformational change of CPO, which are favorable to the substrate access. The analysis of kinetic parameters indicated that the activation was mainly due to an increase in kcat values. The affinity and specificity of CPO to substrates were also improved in these metal ion media. The results in this work are promising in view of industrial applications of this versatile biological catalyst. [source] From cofactor to enzymes.THE CHEMICAL RECORD, Issue 6 2001-phosphate-dependent enzymes, The molecular evolution of pyridoxal- Abstract The pyridoxal-5,-phosphate (vitamin B6)-dependent enzymes that act on amino acid substrates have multiple evolutionary origins. Thus, the common mechanistic features of B6 enzymes are not accidental historical traits but reflect evolutionary or chemical necessities. The B6 enzymes belong to four independent evolutionary lineages of paralogous proteins, of which the , family (with aspartate aminotransferase as the prototype enzyme) is by far the largest and most diverse. The considerably smaller , family (tryptophan synthase , as the prototype enzyme) is structurally and functionally more homogenous. Both the D -alanine aminotransferase family and the alanine racemase family consist of only a few enzymes. The primordial pyridoxal-5,-phosphate-dependent protein catalysts apparently first diverged into reaction-specific protoenzymes, which then diverged further by specializing for substrate specificity. Aminotransferases as well as amino acid decarboxylases are found in two different evolutionary lineages, providing examples of convergent enzyme evolution. The functional specialization of most B6 enzymes seems to have already occurred in the universal ancestor cell before the divergence of eukaryotes, archebacteria, and eubacteria 1500 million years ago. Pyridoxal-5,-phosphate must have emerged very early in biological evolution; conceivably, metal ions and organic cofactors were the first biological catalysts. To simulate particular steps of molecular evolution, both the substrate and reaction specificity of existent B6 enzymes were changed by substitution of active-site residues, and monoclonal pyridoxal-5,-phosphate-dependent catalytic antibodies were produced with selection criteria that might have been operative in the evolution of protein-assisted pyridoxal catalysis. © 2001 John Wiley & Sons, Inc. and The Japan Chemical Journal Forum Chem Rec 1:436,447, 2001 [source] Engineering Allosteric Regulation into Biological CatalystsCHEMBIOCHEM, Issue 18 2009Jacques Fastrez Prof. Abstract Enzymes and ribozymes constitute two classes of biological catalysts. The activity of many natural enzymes is regulated by the binding of ligands that have different structures than their substrates; these ligands are consequently called allosteric effectors. In most allosteric enzymes, the allosteric binding site lies far away from the active site. This implies that communication pathways must exist between these sites. While mechanisms of allosteric regulation were developed more than forty years ago, they continue to be revisited regularly. The improved understanding of these mechanisms has led in the past two decades to projects to transform several unregulated enzymes into allosterically regulated ones either by rational design or directed evolution techniques. More recently, ribozymes have also been the object of similar successful engineering efforts. In this review, after briefly summarising recent progress in the theories of allosteric regulation, several strategies to engineer allosteric regulations in enzymes and ribozymes are described and compared. These redesigned biological catalysts find applications in a variety of areas. [source] | ||||||||||