{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T03:14:19Z","timestamp":1776741259765,"version":"3.51.2"},"reference-count":72,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2011,11,11]],"date-time":"2011-11-11T00:00:00Z","timestamp":1320969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,11,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tuberculosis (TB) is a chronic infectious disease caused mainly by Mycobacterium tuberculosis. The worldwide emergence of drug-resistant strains, the increasing number of infected patients among immune compromised populations, and the large number of latent infected individuals that are reservoir to the disease have underscored the urgent need of new strategies to treat TB. The nucleotide metabolism pathways provide promising molecular targets for the development of novel drugs against active TB and may, hopefully, also be effective against latent forms of the pathogen. The orotate phosphoribosyltransferase (OPRT) enzyme of the de novopyrimidine synthesis pathway catalyzes the reversible phosphoribosyl transfer from 5\u2032-phospho-\u03b1-d-ribose 1\u2032-diphosphate (PRPP) to orotic acid (OA), forming pyrophosphate and orotidine 5\u2032-monophosphate (OMP). Here we describe cloning and characterization of pyrE-encoded protein of M. tuberculosisH37Rv strain as a homodimeric functional OPRTenzyme. The M. tuberculosisOPRT true kinetic constants for forward reaction and product inhibition results suggest a Mono-Iso Ordered Bi\u2013Bi kinetic mechanism, which has not been previously described for this enzyme family. Absence of detection of half reaction and isothermal titration calorimetry (ITC) data support the proposed mechanism. ITC data also provided thermodynamic signatures of non-covalent interactions between substrate\/product and M. tuberculosisOPRT. These data provide a solid foundation on which to base target-based rational design of anti-TB agents and should inform us how to better design inhibitors of M. tuberculosisOPRT.<\/jats:p>\n                  <jats:p\/>","DOI":"10.1039\/c1mb05402c","type":"journal-article","created":{"date-parts":[[2011,11,11]],"date-time":"2011-11-11T07:31:21Z","timestamp":1320996681000},"page":"572-586","source":"Crossref","is-referenced-by-count":21,"title":["Molecular, kinetic and thermodynamic characterization of\n                    <i>Mycobacterium<\/i>\n                    <i>tuberculosis<\/i>\n                    orotate phosphoribosyltransferase"],"prefix":"10.1093","volume":"8","author":[{"given":"Ardala","family":"Breda","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Biologia Celular e Molecular, Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul c , Porto Alegre, Rio Grande do Sul Brazil"},{"name":"Centro de Pesquisas em Biologia Molecular e Funcional, Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul b , Avenida Ipiranga 6900 Pr\u00e9dio 92A \u2013 TECNOPUC 90619-900 Porto Alegre Rio Grande do Sul Brazil \u00a0 luiz.basso@pucrs.br \u00a0 diogenes@pucrs.br \u00a0 +55 51 3320 3629 \u00a0 +55 51 3320 3629"},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia em Tuberculose, Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul a , Porto Alegre, Rio Grande do Sul Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo Astolfi","family":"Rosado","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Medicina e Ci\u00eancias da Sa\u00fade, Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul d , Porto Alegre, Rio Grande do Sul Brazil"},{"name":"Centro de Pesquisas em Biologia Molecular e Funcional, Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul b , Avenida Ipiranga 6900 Pr\u00e9dio 92A \u2013 TECNOPUC 90619-900 Porto Alegre Rio Grande do Sul Brazil \u00a0 luiz.basso@pucrs.br \u00a0 diogenes@pucrs.br \u00a0 +55 51 3320 3629 \u00a0 +55 51 3320 3629"},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia em Tuberculose, Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul a , Porto Alegre, Rio Grande do Sul Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel Macedo","family":"Lorenzini","sequence":"additional","affiliation":[{"name":"Centro de Pesquisas em Biologia Molecular e Funcional, Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul b , Avenida Ipiranga 6900 Pr\u00e9dio 92A \u2013 TECNOPUC 90619-900 Porto Alegre Rio Grande do Sul Brazil \u00a0 luiz.basso@pucrs.br \u00a0 diogenes@pucrs.br \u00a0 +55 51 3320 3629 \u00a0 +55 51 3320 3629"},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia em Tuberculose, Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul a , Porto Alegre, Rio Grande do Sul Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luiz Augusto","family":"Basso","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Biologia Celular e Molecular, Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul c , Porto Alegre, Rio Grande do Sul Brazil"},{"name":"Centro de Pesquisas em Biologia Molecular e Funcional, Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul b , Avenida Ipiranga 6900 Pr\u00e9dio 92A \u2013 TECNOPUC 90619-900 Porto Alegre Rio Grande do Sul Brazil \u00a0 luiz.basso@pucrs.br \u00a0 diogenes@pucrs.br \u00a0 +55 51 3320 3629 \u00a0 +55 51 3320 3629"},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia em Tuberculose, Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul a , Porto Alegre, Rio Grande do Sul Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di\u00f3genes Santiago","family":"Santos","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Biologia Celular e Molecular, Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul c , Porto Alegre, Rio Grande do Sul Brazil"},{"name":"Centro de Pesquisas em Biologia Molecular e Funcional, Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul b , Avenida Ipiranga 6900 Pr\u00e9dio 92A \u2013 TECNOPUC 90619-900 Porto Alegre Rio Grande do Sul Brazil \u00a0 luiz.basso@pucrs.br \u00a0 diogenes@pucrs.br \u00a0 +55 51 3320 3629 \u00a0 +55 51 3320 3629"},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia em Tuberculose, Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul a , Porto Alegre, Rio Grande do Sul Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2011,11,11]]},"reference":[{"key":"2026012913035512300_cit1","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1590\/S0074-02762006000700001","article-title":"et al.","volume":"101","author":"Ducati","year":"2006","journal-title":"Mem. 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