Protein-ribofuranosyl interactions activate orotidine 5′-monophosphate decarboxylase for catalysis
| dc.creator | Judith R. Cristobal | |
| dc.creator | Tiago Antônio da Silva Brandão | |
| dc.creator | Archie C. Reyes | |
| dc.creator | John P. Richard | |
| dc.date.accessioned | 2023-09-29T12:08:00Z | |
| dc.date.accessioned | 2025-09-09T01:23:49Z | |
| dc.date.available | 2023-09-29T12:08:00Z | |
| dc.date.issued | 2021 | |
| dc.identifier.doi | https://doi.org/10.1021/acs.biochem.1c00589 | |
| dc.identifier.issn | 1520-4995 | |
| dc.identifier.uri | https://hdl.handle.net/1843/59026 | |
| dc.language | eng | |
| dc.publisher | Universidade Federal de Minas Gerais | |
| dc.relation.ispartof | Biochemistry | |
| dc.rights | Acesso Restrito | |
| dc.subject | Proteinas | |
| dc.subject | Análise enzimática | |
| dc.subject | Cinética de enzimas | |
| dc.subject | Mecanismos de reações orgânicas | |
| dc.subject | Reações químicas | |
| dc.subject | Bioquímica | |
| dc.subject.other | Chemical reactions | |
| dc.subject.other | Kinetic parameters | |
| dc.subject.other | Organic reactions | |
| dc.subject.other | Peptides and proteins | |
| dc.subject.other | Stabilization | |
| dc.title | Protein-ribofuranosyl interactions activate orotidine 5′-monophosphate decarboxylase for catalysis | |
| dc.type | Artigo de periódico | |
| local.citation.epage | 3373 | |
| local.citation.issue | 45 | |
| local.citation.spage | 3362 | |
| local.citation.volume | 60 | |
| local.description.resumo | 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. | |
| local.identifier.orcid | https://orcid.org/0000-0002-7783-3014 | |
| local.identifier.orcid | https://orcid.org/0000-0001-9955-393X | |
| local.identifier.orcid | https://orcid.org/0000-0002-0440-2387 | |
| local.publisher.country | Brasil | |
| local.publisher.department | ICX - DEPARTAMENTO DE QUÍMICA | |
| local.publisher.initials | UFMG | |
| local.url.externa | https://pubs.acs.org/doi/10.1021/acs.biochem.1c00589 |
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