{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T12:48:00Z","timestamp":1785847680952,"version":"3.56.0"},"reference-count":74,"publisher":"American Chemical Society (ACS)","issue":"15","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007904","name":"Texas A and M University","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100007904","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The pathogen Mycobacterium tuberculosis (Mtb) relies on extensive metabolic remodeling and post-translational regulation of its proteins to retain persistence in its host, yet these biochemical functions remain largely uncharacterized, including the actions of lysine deacylases. Here, we characterized Rv1151c, the sole annotated NAD+-dependent deacylase in Mtb, which we designate Mt-Sirt. Using synthetic substrates, peptide libraries, and mutational analysis, we showed that Mt-Sirt exhibits strong selectivity for peptide substrates containing N\u03b5-succinyl-lysine and long-chain fatty-acyl-lysine groups. Substitution of conserved active-site residues (Y53F and R56M) confirmed their roles in substrate recognition and acyl-group discrimination. Inhibition studies revealed that nicotinamide, NADH, ADP-ribose, and mechanism-based thioamide\/thiourea analogs inhibited Mt-Sirt activity with low-micromolar to nanomolar potency. Initial-velocity, product-inhibition, and dead-end inhibition analyses confirmed that Mt-Sirt operates by an equilibrium-ordered kinetic mechanism in which NAD+ binds first, followed by the N\u03b5-acylated peptide substrate. We further demonstrated that chemically succinylated Mtb isocitrate lyase 1 (ICL1), a key enzyme in Mtb metabolism, was a substrate of Mt-Sirt in vitro. Lastly, metabolic labeling with tetradec-13-ynoic acid (Alk-12) revealed widespread lysine and N-terminal fatty acylation in Mtb cells, suggesting that Mt-Sirt may regulate previously unrecognized fatty-acyl PTMs in vivo. Together, these findings provide a kinetic and substrate-specificity analysis of Mt-Sirt, and highlight its potential role in controlling reversible lysine acylation in Mtb.<\/jats:p>","DOI":"10.1021\/acs.biochem.6c00374","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T16:15:26Z","timestamp":1783959326000},"page":"2400-2418","source":"Crossref","is-referenced-by-count":0,"title":["Substrate Specificity\nand Kinetic Mechanism of the\nNAD+-Dependent Deacylase from\n                    <i>Mycobacterium tuberculosis<\/i>\n                    , Rv1151c (\n                    <i>Mt<\/i>\n                    -Sirt)"],"prefix":"10.1021","volume":"65","author":[{"given":"Drake M.","family":"Mellott","sequence":"first","affiliation":[{"name":"Texas A&M University , , , ,","place":["College Station, Texas, United States, 77843"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8861-5450","authenticated-orcid":true,"given":"Jiyun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Texas A&M University , , , ,","place":["College Station, Texas, United States, 77843"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hudson","family":"Fulcher","sequence":"additional","affiliation":[{"name":"Texas A&M University , , , ,","place":["College Station, Texas, United States, 77843"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1931-8073","authenticated-orcid":true,"given":"Thomas D.","family":"Meek","sequence":"additional","affiliation":[{"name":"Texas A&M University , , , ,","place":["College Station, Texas, United States, 77843"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"2026080408073311200_cit1","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1126\/science.1179687","article-title":"Acetylation of metabolic enzymes\ncoordinates carbon source utilization and metabolic flux","volume":"327","author":"Wang","year":"2010","journal-title":"Science"},{"key":"2026080408073311200_cit2","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1038\/nrm3841","article-title":"The growing\nlandscape of lysine acetylation links metabolism and cell signalling","volume":"15","author":"Choudhary","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2026080408073311200_cit3","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1016\/j.cmet.2017.03.006","article-title":"A Class of Reactive\nAcyl-CoA Species Reveals the Non-enzymatic Origins of Protein Acylation","volume":"25","author":"Wagner","year":"2017","journal-title":"Cell Metab."},{"key":"2026080408073311200_cit4","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1016\/j.bbapap.2010.01.021","article-title":"Sirtuin\nchemical mechanisms","volume":"1804","author":"Sauve","year":"2010","journal-title":"Biochim. Biophys. Acta,\nProteins Proteomics"},{"key":"2026080408073311200_cit5","doi-asserted-by":"publisher","first-page":"9249","DOI":"10.1021\/bi034959l","article-title":"Sir2 Regulation by Nicotinamide Results\nfrom Switching\nbetween Base Exchange and Deacetylation Chemistry","volume":"42","author":"Sauve","year":"2003","journal-title":"Biochemistry"},{"key":"2026080408073311200_cit6","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1146\/annurev.biochem.74.082803.133500","article-title":"The Biochemistry\nof Sirtuins","volume":"75","author":"Sauve","year":"2006","journal-title":"Annu. Rev. Biochem."},{"key":"2026080408073311200_cit7","doi-asserted-by":"publisher","first-page":"50985","DOI":"10.1074\/jbc.M306552200","article-title":"Mechanism of Nicotinamide\nInhibition and Transglycosidation by Sir2 Histone\/Protein Deacetylases\n*","volume":"278","author":"Jackson","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2026080408073311200_cit8","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1146\/annurev-biochem-060815-014537","article-title":"The Substrate Specificity\nof Sirtuins","volume":"85","author":"Bheda","year":"2016","journal-title":"Annu. Rev. Biochem."},{"key":"2026080408073311200_cit9","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1146\/annurev.pathol.4.110807.092250","article-title":"Mammalian Sirtuins:\nBiological Insights and Disease\nRelevance","volume":"5","author":"Haigis","year":"2010","journal-title":"Annu. Rev. Pathol.: Mech. Dis."},{"key":"2026080408073311200_cit10","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1021\/acs.chemrev.7b00181","article-title":"Lysine Acetylation\nGoes Global: From Epigenetics to Metabolism and Therapeutics","volume":"118","author":"Ali","year":"2018","journal-title":"Chem. Rev."},{"key":"2026080408073311200_cit11","first-page":"25","article-title":"Chapter Two\n- Targeting Sirtuins: Substrate Specificity and Inhibitor Design","volume-title":"Progress in Molecular Biology and Translational Science","author":"Rajabi","year":"2018"},{"key":"2026080408073311200_cit12","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1016\/j.chembiol.2020.07.002","article-title":"The Chemical Biology\nof Reversible Lysine Post-translational\nModifications","volume":"27","author":"Wang","year":"2020","journal-title":"Cell Chem. Biol."},{"key":"2026080408073311200_cit13","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1038\/s41579-019-0243-0","article-title":"Protein post-translational modifications\nin bacteria","volume":"17","author":"Macek","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"2026080408073311200_cit14","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.3389\/fmicb.2019.01604","article-title":"Post-translational Protein Acetylation:\nAn Elegant Mechanism for Bacteria to Dynamically Regulate Metabolic\nFunctions","volume":"10","author":"Christensen","year":"2019","journal-title":"Front. Microbiol."},{"key":"2026080408073311200_cit15","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1074\/mcp.M114.045922","article-title":"Succinylome Analysis Reveals the\nInvolvement of Lysine Succinylation in Metabolism in Pathogenic Mycobacterium tuberculosis","volume":"14","author":"Yang","year":"2015","journal-title":"Mol. Cell. Proteomics"},{"key":"2026080408073311200_cit16","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1080\/07391102.2016.1169219","article-title":"Lysine succinylation\nof Mycobacterium tuberculosis isocitrate\nlyase (ICL) fine-tunes the microbial resistance to antibiotics","volume":"35","author":"Zhou","year":"2016","journal-title":"J. Biomol. Struct. Dyn."},{"key":"2026080408073311200_cit17","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.biocel.2014.11.010","article-title":"Proteome-wide lysine acetylation profiling of the human pathogen Mycobacterium tuberculosis","volume":"59","author":"Xie","year":"2015","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"2026080408073311200_cit18","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1021\/acs.jproteome.5b00917","article-title":"Proteome-wide Lysine Glutarylation\nProfiling of the Mycobacterium tuberculosis H37Rv","volume":"15","author":"Xie","year":"2016","journal-title":"J. Proteome Res."},{"key":"2026080408073311200_cit19","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2022.127209","article-title":"Malonylome analysis uncovers the association of lysine malonylation\nwith metabolism and acidic stress in pathogenic Mycobacterium tuberculosis","volume":"265","author":"Bi","year":"2022","journal-title":"Microbiol. Res."},{"key":"2026080408073311200_cit20","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/j.jmb.2004.01.060","article-title":"Structure\nand Substrate Binding Properties\nof cobB, a Sir2 Homolog Protein Deacetylase from Escherichia coli","volume":"337","author":"Zhao","year":"2004","journal-title":"J. Mol. Biol."},{"key":"2026080408073311200_cit21","doi-asserted-by":"publisher","first-page":"3509","DOI":"10.1074\/mcp.M113.031567","article-title":"Identification\nof lysine succinylation substrates and the succinylation\nregulatory enzyme CobB in Escherichia coli","volume":"12","author":"Colak","year":"2013","journal-title":"Mol. Cell. Proteomics"},{"key":"2026080408073311200_cit22","doi-asserted-by":"publisher","first-page":"e01096","DOI":"10.1128\/mBio.01096-17","article-title":"Sirtuin Lipoamidase\nActivity Is Conserved in Bacteria\nas a Regulator of Metabolic Enzyme Complexes","volume":"8","author":"Rowland","year":"2017","journal-title":"mBio"},{"key":"2026080408073311200_cit23","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaw6703","article-title":"Protein lysine\nde-2-hydroxyisobutyrylation\nby CobB in prokaryotes","volume":"5","author":"Dong","year":"2019","journal-title":"Sci. Adv."},{"key":"2026080408073311200_cit24","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1046\/j.1365-2958.2003.03425.x","article-title":"Genes required for mycobacterial\ngrowth defined by high density mutagenesis","volume":"48","author":"Sassetti","year":"2003","journal-title":"Mol. Microbiol."},{"key":"2026080408073311200_cit25","doi-asserted-by":"publisher","first-page":"12989","DOI":"10.1073\/pnas.2134250100","article-title":"Genetic requirements\nfor mycobacterial survival during\ninfection","volume":"100","author":"Sassetti","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026080408073311200_cit26","doi-asserted-by":"publisher","first-page":"e02133","DOI":"10.1128\/mBio.02133-16","article-title":"Comprehensive\nEssentiality Analysis of the Mycobacterium tuberculosis Genome via Saturating Transposon Mutagenesis","volume":"8","author":"DeJesus","year":"2017","journal-title":"mBio"},{"key":"2026080408073311200_cit27","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2318","article-title":"Cyclic AMP\nregulation of protein lysine acetylation in Mycobacterium tuberculosis","volume":"19","author":"Lee","year":"2012","journal-title":"Nat. Struct. Mol.\nBiol."},{"key":"2026080408073311200_cit28","doi-asserted-by":"publisher","first-page":"5883","DOI":"10.1021\/bi200156t","article-title":"Reversible\nacetylation and inactivation\nof Mycobacterium tuberculosis acetyl-CoA\nsynthetase is dependent on cAMP","volume":"50","author":"Xu","year":"2011","journal-title":"Biochemistry"},{"key":"2026080408073311200_cit29","doi-asserted-by":"publisher","DOI":"10.1038\/s41426-018-0112-3","article-title":"Acetylation of lysine 182 inhibits\nthe ability of Mycobacterium tuberculosis DosR to bind DNA and regulate gene expression during hypoxia","volume":"7","author":"Bi","year":"2018","journal-title":"Emerg. Microbes Infect."},{"key":"2026080408073311200_cit30","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1016\/j.jmb.2019.01.004","article-title":"Acetylation\nof Response\nRegulator Proteins, TcrX and MtrA in M. tuberculosis Tunes their Phosphotransfer Ability and Modulates Two-Component\nSignaling Crosstalk","volume":"431","author":"Singh","year":"2019","journal-title":"J. Mol. Biol."},{"key":"2026080408073311200_cit31","doi-asserted-by":"publisher","first-page":"2214","DOI":"10.1021\/acsinfecdis.0c00329","article-title":"Post-translational\nSuccinylation of Mycobacterium tuberculosis Enoyl-CoA Hydratase EchA19 Slows Catalytic Hydration of Cholesterol\nCatabolite 3-Oxo-chol-4,22-diene-24-oyl-CoA","volume":"6","author":"Bonds","year":"2020","journal-title":"ACS Infect. Dis."},{"key":"2026080408073311200_cit32","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1021\/acs.biochem.7b01089","article-title":"Acetylation by Eis and Deacetylation\nby Rv1151c of Mycobacterium tuberculosis HupB: Biochemical and\nStructural Insight","volume":"57","author":"Green","year":"2018","journal-title":"Biochemistry"},{"key":"2026080408073311200_cit33","doi-asserted-by":"publisher","first-page":"22315","DOI":"10.1074\/jbc.M116.744532","article-title":"Post-translational\nAcetylation of MbtA Modulates Mycobacterial Siderophore Biosynthesis","volume":"291","author":"Vergnolle","year":"2016","journal-title":"J. Biol. Chem."},{"key":"2026080408073311200_cit34","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1016\/j.bbrc.2017.09.087","article-title":"A Sir2 family protein\nRv1151c deacetylates HU to alter its DNA binding mode in Mycobacterium tuberculosis","volume":"493","author":"Anand","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2026080408073311200_cit35","doi-asserted-by":"publisher","first-page":"e04002","DOI":"10.1128\/spectrum.04002-22","article-title":"Acetylation of Cyclic\nAMP Receptor\nProtein by Acetyl Phosphate Modulates Mycobacterial Virulence","volume":"11","author":"Di","year":"2023","journal-title":"Microbiol. Spectrum"},{"key":"2026080408073311200_cit36","doi-asserted-by":"publisher","first-page":"4967","DOI":"10.1021\/ja810122f","article-title":"Robust Fluorescent Detection of Protein\nFatty-Acylation with Chemical Reporters","volume":"131","author":"Charron","year":"2009","journal-title":"J.\nAm. Chem. Soc."},{"key":"2026080408073311200_cit37","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1021\/acschembio.0c00740","article-title":"Covalent Inactivation\nof Mycobacterium tuberculosis Isocitrate\nLyase by cis-2,3-Epoxy-Succinic Acid","volume":"16","author":"Pham","year":"2021","journal-title":"ACS Chem.\nBiol."},{"key":"2026080408073311200_cit38","doi-asserted-by":"publisher","first-page":"17666","DOI":"10.1021\/jacs.1c07970","article-title":"Mechanism-Based\nInactivation of Mycobacterium tuberculosis Isocitrate Lyase 1 by (2R,3S)-2-Hydroxy-3-(nitromethyl)succinic\nacid","volume":"143","author":"Mellott","year":"2021","journal-title":"J. Am. Chem. Soc."},{"key":"2026080408073311200_cit39","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1021\/acschembio.0c00875","article-title":"A Clinical-Stage\nCysteine Protease Inhibitor blocks SARS-CoV-2 Infection of Human and\nMonkey Cells","volume":"16","author":"Mellott","year":"2021","journal-title":"ACS Chem. Biol."},{"key":"2026080408073311200_cit40","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein\nstructure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"2026080408073311200_cit41","doi-asserted-by":"publisher","first-page":"D439","DOI":"10.1093\/nar\/gkab1061","article-title":"AlphaFold Protein Structure Database:\nmassively expanding the structural coverage of protein-sequence space\nwith high-accuracy models","volume":"50","author":"Varadi","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"2026080408073311200_cit42","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2500A\nvisualization\nsystem for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"2026080408073311200_cit43","doi-asserted-by":"publisher","first-page":"11142","DOI":"10.1002\/anie.202002899","article-title":"Evolved, Selective\nErasers of Distinct Lysine Acylations","volume":"59","author":"Spinck","year":"2020","journal-title":"Angew.\nChem., Int. Ed."},{"key":"2026080408073311200_cit44","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1126\/science.1207861","article-title":"Sirt5 is a\nNAD-dependent protein lysine demalonylase and desuccinylase","volume":"334","author":"Du","year":"2011","journal-title":"Science (New York, N.Y.)"},{"key":"2026080408073311200_cit45","doi-asserted-by":"publisher","first-page":"31350","DOI":"10.1074\/jbc.C113.511261","article-title":"Activation\nof the Protein Deacetylase\nSIRT6 by Long-chain Fatty Acids and Widespread Deacylation by Mammalian\nSirtuins","volume":"288","author":"Feldman","year":"2013","journal-title":"J. Biol. Chem."},{"key":"2026080408073311200_cit46","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1002\/pro.2546","article-title":"Alternate\ndeacylating specificities\nof the archaeal sirtuins Sir2Af1 and Sir2Af2","volume":"23","author":"Ringel","year":"2014","journal-title":"Protein Sci."},{"key":"2026080408073311200_cit47","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1134\/S0006297909070062","article-title":"Cloning\nand characterization\nof NAD-dependent protein deacetylase (Rv1151c) from Mycobacterium tuberculosis","volume":"74","author":"Gu","year":"2009","journal-title":"Biochemistry (Moscow)"},{"key":"2026080408073311200_cit48","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/nature12038","article-title":"SIRT6 regulates\nTNF-\u03b1 secretion through hydrolysis of long-chain fatty acyl\nlysine","volume":"496","author":"Jiang","year":"2013","journal-title":"Nature"},{"key":"2026080408073311200_cit49","doi-asserted-by":"publisher","DOI":"10.1038\/srep08529","article-title":"Efficient\nDemyristoylase Activity\nof SIRT2 Revealed by Kinetic and Structural Studies","volume":"5","author":"Teng","year":"2015","journal-title":"Sci. Rep."},{"key":"2026080408073311200_cit50","doi-asserted-by":"publisher","first-page":"3019","DOI":"10.1002\/1873-3468.12345","article-title":"Crystal structures\nof SIRT3 reveal that the \u03b12-\u03b13 loop and \u03b13-helix\naffect the interaction with long-chain acyl lysine","volume":"590","author":"Gai","year":"2016","journal-title":"FEBS Lett."},{"key":"2026080408073311200_cit51","doi-asserted-by":"publisher","first-page":"28307","DOI":"10.1074\/jbc.M112.384511","article-title":"The bicyclic intermediate structure\nprovides insights into the desuccinylation mechanism of human sirtuin\n5 (SIRT5), The","volume":"287","author":"Zhou","year":"2012","journal-title":"J. Biol. Chem."},{"key":"2026080408073311200_cit52","doi-asserted-by":"publisher","first-page":"14836","DOI":"10.1002\/anie.201709050","article-title":"Mechanism-Based\nInhibitors of the\nHuman Sirtuin 5 Deacylase: Structure-Activity Relationship, Biostructural,\nand Kinetic Insight","volume":"56","author":"Rajabi","year":"2017","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026080408073311200_cit53","doi-asserted-by":"publisher","first-page":"1922","DOI":"10.1021\/ja2090417","article-title":"Thiosuccinyl\nPeptides as Sirt5-Specific Inhibitors","volume":"134","author":"He","year":"2012","journal-title":"J. Am.\nChem. Soc."},{"key":"2026080408073311200_cit54","doi-asserted-by":"publisher","first-page":"14478","DOI":"10.1021\/bi7013294","article-title":"Mechanism-Based\nInhibition of Sir2 Deacetylases by\nThioacetyl-Lysine Peptide","volume":"46","author":"Smith","year":"2007","journal-title":"Biochemistry"},{"key":"2026080408073311200_cit55","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1055\/s-0036-1591842","article-title":"T3P \u2013 A Benign\nDesulfurating Reagent in the Synthesis of Isothiocyanates","volume":"50","author":"Janczewski","year":"2018","journal-title":"Synthesis"},{"key":"2026080408073311200_cit56","doi-asserted-by":"publisher","first-page":"4131","DOI":"10.1021\/acs.jmedchem.9b00191","article-title":"Novel Lysine-Based Thioureas as Mechanism-Based Inhibitors of Sirtuin\n2 (SIRT2) with Anticancer Activity in a Colorectal Cancer Murine Model","volume":"62","author":"Farooqi","year":"2019","journal-title":"J. Med. Chem."},{"key":"2026080408073311200_cit57","doi-asserted-by":"publisher","first-page":"1886","DOI":"10.1021\/acsmedchemlett.9b00580","article-title":"Dethioacylation\nby Sirtuins 1\u20133:\nConsiderations for Drug Design Using Mechanism-Based Sirtuin Inhibition","volume":"11","author":"Rajabi","year":"2020","journal-title":"ACS Med. Chem. Lett."},{"key":"2026080408073311200_cit58","doi-asserted-by":"publisher","first-page":"9877","DOI":"10.1021\/bi049592e","article-title":"Substrate Specificity\nand Kinetic Mechanism of the Sir2 Family of NAD+-Dependent Histone\/Protein\nDeacetylases","volume":"43","author":"Borra","year":"2004","journal-title":"Biochemistry"},{"key":"2026080408073311200_cit59","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1016\/S0021-9258(17)49896-6","article-title":"Mechanism\nof activation for the sirtuin 6 protein deacylase","volume":"295","author":"Klein","year":"2020","journal-title":"J. Biol. Chem."},{"key":"2026080408073311200_cit60","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1016\/j.molcel.2005.02.022","article-title":"Mechanism\nof Sirtuin Inhibition by\nNicotinamide: Altering the NAD Cosubstrate Specificity of a Sir2 Enzyme","volume":"17","author":"Avalos","year":"2005","journal-title":"Mol. Cell"},{"key":"2026080408073311200_cit61","doi-asserted-by":"publisher","first-page":"15456","DOI":"10.1021\/bi011858j","article-title":"Chemistry of Gene Silencing: The\nMechanism of NAD+-Dependent\nDeacetylation Reactions","volume":"40","author":"Sauve","year":"2001","journal-title":"Biochemistry"},{"key":"2026080408073311200_cit62","doi-asserted-by":"publisher","first-page":"45099","DOI":"10.1074\/jbc.M205670200","article-title":"Inhibition of Silencing and Accelerated\nAging by Nicotinamide,\na Putative Negative Regulator of Yeast Sir2 and Human SIRT1 *","volume":"277","author":"Bitterman","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2026080408073311200_cit63","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1111\/j.1365-2958.2006.05155.x","article-title":"Role of the methylcitrate\ncycle in Mycobacterium tuberculosis metabolism, intracellular growth, and virulence","volume":"60","author":"Mun\u0303oz-Eli\u0301as","year":"2006","journal-title":"Mol. Microbiol."},{"key":"2026080408073311200_cit64","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1038\/35021074","article-title":"Persistence\nof Mycobacterium tuberculosis in macrophages and mice requires the\nglyoxylate shunt enzyme isocitrate lyase","volume":"406","author":"McKinney","year":"2000","journal-title":"Nature"},{"key":"2026080408073311200_cit65","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1021\/pr500859a","article-title":"First succinyl-proteome\nprofiling of extensively drug-resistant Mycobacterium tuberculosis revealed involvement of succinylation\nin cellular physiology","volume":"14","author":"Xie","year":"2015","journal-title":"J. Proteome Res."},{"key":"2026080408073311200_cit66","doi-asserted-by":"publisher","first-page":"9934","DOI":"10.1093\/nar\/gkz724","article-title":"Structural\nand functional insight into the Mycobacterium tuberculosis protein PrpR reveals a\nnovel type of transcription factor","volume":"47","author":"Tang","year":"2019","journal-title":"Nucleic\nAcids Res."},{"key":"2026080408073311200_cit67","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.2826","article-title":"Global\nprofiling of lysine reactivity and ligandability\nin the human proteome","volume":"9","author":"Hacker","year":"2017","journal-title":"Nat. Chem."},{"key":"2026080408073311200_cit68","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1038\/77964","article-title":"Structure\nof isocitrate lyase, a\npersistence factor of Mycobacterium tuberculosis","volume":"7","author":"Sharma","year":"2000","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2026080408073311200_cit69","doi-asserted-by":"publisher","first-page":"7617","DOI":"10.1073\/pnas.1706134114","article-title":"Mechanism-based\ninactivator of isocitrate lyases 1 and 2 from Mycobacterium tuberculosis","volume":"114","author":"Pham","year":"2017","journal-title":"Proc. Natl. Acad.\nSci. U.S.A."},{"key":"2026080408073311200_cit70","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1107\/S1744309108031679","article-title":"Rv0802c from Mycobacterium tuberculosis: the first structure of a succinyltransferase\nwith the GNAT fold","volume":"64","author":"Vetting","year":"2008","journal-title":"Acta Crystallogr., Sect.\nF:Struct. Biol. Cryst. Commun."},{"key":"2026080408073311200_cit71","doi-asserted-by":"crossref","unstructured":"Anand, C.; Santoshi, M.; Singh, P. R.; Nagaraja, V.\n          Rv0802c is an\nacyltransferase that succinylates and acetylates Mycobacterium tuberculosis nucleoid-associated protein HU\n          Microbiology\n          2021; Vol. 16710.1099\/mic.0.001058.","DOI":"10.1099\/mic.0.001058"},{"key":"2026080408073311200_cit72","doi-asserted-by":"publisher","first-page":"6309","DOI":"10.1016\/j.vaccine.2006.05.097","article-title":"Mycobacterium tuberculosis \u0394RD1 \u0394panCD: A safe and limited\nreplicating mutant strain that protects immunocompetent and immunocompromised\nmice against experimental tuberculosis","volume":"24","author":"Sambandamurthy","year":"2006","journal-title":"Vaccine"},{"key":"2026080408073311200_cit73","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1111\/j.1365-2958.2008.06274.x","article-title":"Growth of Mycobacterium tuberculosis biofilms containing free mycolic acids\nand harbouring drug-tolerant bacteria","volume":"69","author":"Ojha","year":"2008","journal-title":"Mol.\nMicrobiol."},{"key":"2026080408073311200_cit74","first-page":"191","article-title":"Chapter Seven - Use of alkyne-tagged\nmyristic acid to detect N-terminal myristoylation","volume-title":"Methods Enzymol.","author":"Xu","year":"2023"}],"container-title":["Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.biochem.6c00374","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/bichaw\/article-pdf\/65\/15\/2400\/65894558\/acs.biochem.6c00374.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/bichaw\/article-pdf\/65\/15\/2400\/65894558\/acs.biochem.6c00374.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T12:14:11Z","timestamp":1785845651000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/bichaw\/article\/65\/15\/2400\/5207596\/Substrate-Specificity-and-Kinetic-Mechanism-of-the"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,13]]},"references-count":74,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,7,13]]},"published-print":{"date-parts":[[2026,8,4]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.biochem.6c00374","relation":{},"ISSN":["0006-2960","1520-4995"],"issn-type":[{"value":"0006-2960","type":"print"},{"value":"1520-4995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,13]]}}}