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http://hdl.handle.net/1843/59026| Type: | Artigo de Periódico |
| Title: | Protein-ribofuranosyl interactions activate orotidine 5′-monophosphate decarboxylase for catalysis |
| Authors: | Judith R. Cristobal Tiago Antônio da Silva Brandão Archie C. Reyes John P. Richard |
| Abstract: | The role of a global, substrate-driven, enzyme conformational change in enabling the extraordinarily large rate acceleration for orotidine 5′-monophosphate decarboxylase (OMPDC)-catalyzed decarboxylation of orotidine 5′-monophosphate(OMP) is examined in experiments that focus on the interactions between OMPDC and the ribosyl hydroxyl groups ofOMP. TheD37 and T100′side chains of OMPDC interact, respectively, with the C-3′and C-2′hydroxyl groups of enzyme-boundOMP.D37G and T100′A substitutions result in 1.4 kcal/mol increases in the activation barrier ΔG⧧for catalysis of decarboxylation of thephosphodianion-truncated substrate 1-(β-D-erythrofuranosyl) orotic acid (EO) but result in larger 2.1−2.9 kcal/mol increases in ΔG⧧for decarboxylation of OMPand for phosphite dianion-activated decarboxylation of EO. This shows that these substitutions reduce transition-state stabilization by the Q215, Y217, and R235 side chains at the dianion binding site. The D37G and T100′A substitutions result in <1.0 kcal/mol increases in ΔG⧧ for activation of OMPDC-catalyzed decarboxylation of the phosphoribofuranosyl-truncated substrate FO by phosphite dianions. Experiments to probe the effect of D37 and T100′substitutions on the kinetic parameters for D-glycerol 3-phosphate and D-erythritol 4-phosphate activators of OMPDC-catalyzed decarboxylation of FO show that ΔG⧧for sugar phosphate-activated reactions is increased byca.2.5 kcal/mol for each −OH interaction eliminated by D37G or T100′A substitutions. We conclude that the interactions between the D37 and T100′side chainsand ribosyl or ribosyl-like hydroxyl groups are utilized to activate OMPDC for catalysis of decarboxylation of OMP, EO, and FO. |
| Subject: | Proteinas Análise enzimática Cinética de enzimas Mecanismos de reações orgânicas Reações químicas Bioquímica |
| language: | eng |
| metadata.dc.publisher.country: | Brasil |
| Publisher: | Universidade Federal de Minas Gerais |
| Publisher Initials: | UFMG |
| metadata.dc.publisher.department: | ICX - DEPARTAMENTO DE QUÍMICA |
| Rights: | Acesso Restrito |
| metadata.dc.identifier.doi: | https://doi.org/10.1021/acs.biochem.1c00589 |
| URI: | http://hdl.handle.net/1843/59026 |
| Issue Date: | 2021 |
| metadata.dc.url.externa: | https://pubs.acs.org/doi/10.1021/acs.biochem.1c00589 |
| metadata.dc.relation.ispartof: | Biochemistry |
| Appears in Collections: | Artigo de Periódico |
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