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Insight into cofactor recognition in arylamine N-acetyltransferase enzymes: structure of Mesorhizobium loti arylamine N-acetyltransferase in complex with coenzyme A.

Xu X, Li de la Sierra-Gallay I, Kubiak X, Duval R, Chaffotte AF, Dupret JM, Haouz A, Rodrigues-Lima F
Acta Crystallogr D Biol Crystallogr 71 266-73 (2015)
Cited: 7 times
EuropePMC logo PMID: 25664736

Abstract

Arylamine N-acetyltransferases (NATs) are xenobiotic metabolizing enzymes that catalyze the acetyl-CoA-dependent acetylation of arylamines. To better understand the mode of binding of the cofactor by this family of enzymes, the structure of Mesorhizobium loti NAT1 [(RHILO)NAT1] was determined in complex with CoA. The F42W mutant of (RHILO)NAT1 was used as it is well expressed in Escherichia coli and displays enzymatic properties similar to those of the wild type. The apo and holo structures of (RHILO)NAT1 F42W were solved at 1.8 and 2 Å resolution, respectively. As observed in the Mycobacterium marinum NAT1-CoA complex, in (RHILO)NAT1 CoA binding induces slight structural rearrangements that are mostly confined to certain residues of its `P-loop'. Importantly, it was found that the mode of binding of CoA is highly similar to that of M. marinum NAT1 but different from the modes reported for Bacillus anthracis NAT1 and Homo sapiens NAT2. Therefore, in contrast to previous data, this study shows that different orthologous NATs can bind their cofactors in a similar way, suggesting that the mode of binding CoA in this family of enzymes is less diverse than previously thought. Moreover, it supports the notion that the presence of the `mammalian/eukaryotic insertion loop' in certain NAT enzymes impacts the mode of binding CoA by imposing structural constraints.

Articles - 4nv7 mentioned but not cited (2)

  1. Comparative Investigation of 15 Xenobiotic-Metabolizing N-Acetyltransferase (NAT) Homologs from Bacteria. Garefalaki V, Papavergi MG, Savvidou O, Papanikolaou G, Felföldi T, Márialigeti K, Fakis G, Boukouvala S. Appl Environ Microbiol 87 e0081921 (2021)
  2. PtmC Catalyzes the Final Step of Thioplatensimycin, Thioplatencin, and Thioplatensilin Biosynthesis and Expands the Scope of Arylamine N-Acetyltransferases. Zheng CJ, Kalkreuter E, Fan BY, Liu YC, Dong LB, Shen B. ACS Chem Biol 16 96-105 (2021)


Articles citing this publication (5)

  1. Identification of cancer chemopreventive isothiocyanates as direct inhibitors of the arylamine N-acetyltransferase-dependent acetylation and bioactivation of aromatic amine carcinogens. Duval R, Xu X, Bui LC, Mathieu C, Petit E, Cariou K, Dodd RH, Dupret JM, Rodrigues-Lima F. Oncotarget 7 8688-8699 (2016)
  2. Xenobiotic-metabolizing enzymes in Bacillus anthracis: molecular and functional analysis of a truncated arylamine N-acetyltransferase isozyme. Kubiak X, Duval R, Pluvinage B, Chaffotte AF, Dupret JM, Rodrigues-Lima F. Br J Pharmacol 174 2174-2182 (2017)
  3. A unique GCN5-related glucosamine N-acetyltransferase region exist in the fungal multi-domain glycoside hydrolase family 3 β-N-acetylglucosaminidase. Qin Z, Xiao Y, Yang X, Mesters JR, Yang S, Jiang Z. Sci Rep 5 18292 (2015)
  4. The actinobacterium Tsukamurella paurometabola has a functionally divergent arylamine N-acetyltransferase (NAT) homolog. Garefalaki V, Kontomina E, Ioannidis C, Savvidou O, Vagena-Pantoula C, Papavergi MG, Olbasalis I, Patriarcheas D, Fylaktakidou KC, Felföldi T, Márialigeti K, Fakis G, Boukouvala S. World J Microbiol Biotechnol 35 174 (2019)
  5. Biochemical Characterization of Arylamine N-acetyltransferases From Vibrio vulnificus. Liu X, Liu Y, Zhao G, Zhang Y, Liu L, Wang J, Wang Y, Zhang S, Li X, Guo D, Wang P, Xu X. Front Microbiol 11 595083 (2020)


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