Structure and Functional Diversity of GCN5-Related N-Acetyltransferases (GNAT)

Ud-Din, Abu Iftiaf Md Salah; Tikhomirova, Alexandra; Roujeinikova, Anna

doi:10.3390/ijms17071018

Cited by 128 publications

(107 citation statements)

References 216 publications

(456 reference statements)

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“…The Gcn5-related N -acetyltransferase (GNAT) superfamily consists of evolutionarily related acetyltransferases from all kingdoms of life [1-3]. GNATs catalyze the transfer of an acyl group from acyl-coenzyme A (most often acetyl-coenzyme A (AcCoA)) to a primary amine or hydroxyl group, but the range of observed substrates is very wide.…”

Section: Introductionmentioning

confidence: 99%

“…GNATs catalyze the transfer of an acyl group from acyl-coenzyme A (most often acetyl-coenzyme A (AcCoA)) to a primary amine or hydroxyl group, but the range of observed substrates is very wide. GNAT substrates include aminoglycoside antibiotics, polyamines, arylalkylamines, glucosamine-6-phosphate, and other small molecules [3]. GNATs are also involved in protein acetylation, including both N-terminal ( N α) acetylation of protein and peptide termini and N -epsilon ( N ε) acetylation of internal lysine residues [2-6].…”

Section: Introductionmentioning

confidence: 99%

“…A number of GNATs have been structurally characterized and many reveal very interesting features such as different forms of dimer formation and numerous variants of domain swapping [3]. One approach we have used to identify possible substrates for structural and functional studies of uncharacterized GNATs is to screen them using a broad-substrate-screening assay [7].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Insight into the 3D structure and substrate specificity of previously uncharacterized GNAT superfamily acetyltransferases from pathogenic bacteria

Majorek

Osinski

Tran

et al. 2017

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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Members of Gcn5-related N-acetyltransferase (GNAT) superfamily catalyze the acetylation of a wide range of small molecule and protein substrates. Due to their abundance in all kingdoms of life and diversity of their functions, they are implicated in many aspects of eukaryotic and prokaryotic physiology. Although numerous GNATs have been identified thus far, many remain structurally and functionally uncharacterized. The elucidation of their structures and functions is critical for broadening our knowledge of this diverse and important superfamily. In this work, we present the structural and kinetic analyses of two previously uncharacterized bacterial acetyltransferases - SACOL1063 from Staphylococcus aureus strain COL and CD1211 from Clostridium difficile strain 630. Our structures of SACOL1063 show substantial flexibility of a loop that is likely responsible for substrate recognition and binding compared to structures of other homologs. In the CoA complex structure, we found two CoA molecules bound in both the canonical AcCoA/CoA-binding site and the acceptor-substrate-binding site. Our work also provides initial clues regarding the substrate specificity of these two enzymes; however, their native function(s) remain unknown. We found both proteins act as N-rather than O-acetyltransferases and preferentially acetylate L-threonine. The combination of structural and kinetic analyses of these two previously uncharacterized GNATs provides fundamental knowledge and a framework on which future studies can be built to elucidate their native functions.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Insight into the 3D structure and substrate specificity of previously uncharacterized GNAT superfamily acetyltransferases from pathogenic bacteria

Majorek

Osinski

Tran

et al. 2017

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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“…1B). Residues 423-592 of MmEsco2 368-592 reveal an overall fold similar to that of other GNAT family acetyltransferases 40 . This fold consists of a conserved catalytic domain (β5, β6, β7, α3, and α4), which is flanked by structurally variable regions (Fig.…”

Section: Structure Of Mmesco2 368-592 In Complex With Coenzyme Amentioning

confidence: 69%

Alternative catalytic residues in the active site of Esco acetyltransferases

Ajam

Petkau

et al. 2019

Preprint

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Cohesin is a protein complex encircles the DNA and regulates the separation of sister chromatids during cell division. Following a catalytic mechanism that is insufficiently understood, Esco1 and Esco2 acetyltransferases acetylate Smc3 subunit of cohesin, thereby inducing a stabilization of cohesin on DNA. As a prerequisite for structureguided investigation of enzymatic activity, we determine here the crystal structure of the mouse Esco2/CoA complex at 1.8 Å resolution. We reconstitute the entire cohesin as a tetrameric assembly and use it as a physiologically-relevant substrate for enzymatic assays in vitro. Furthermore, we employ cell-based complementation studies in mouse embryonic fibroblast deficient for Esco1 and Esco2, as a means to identify catalytically-important residues in vivo. These analyses demonstrate that D567/S566 and E491/S527, located on opposite sides of the MmEsco2 active site cleft, are critical for catalysis. Our experiments supports a catalytic mechanism of acetylation where residues D567 and E491 are general bases that deprotonate the εamino group of lysine substrate, via two nearby serine residues -S566 and S527-that possess a proton relay function.

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“…Examination of the identified genes, highlighted two acetyltransferases of the Gcn5-related N-acetyltransferases family (GNAT) 58 , 10 transcription factor-associated genes, and 14 genes encoding membrane proteins. GNAT enzymes catalyze the transfer of an acyl moiety from acyl coenzyme A (acyl-CoA) to a large number of different substrates and are essential for lipid biosynthesis 59 . Here, the two acetyltransferases (Brasy3G100400 and Brasy9G171000 - Fig.…”

Section: Genetic Algorithm (Ga) Identifies Accession-specific Transcrmentioning

confidence: 99%

Correlation-based network analysis combined with machine learning techniques highlight the role of the GABA shunt in Brachypodium sylvaticum freezing tolerance

Toubiana

Sade

Liu

et al. 2020

Sci Rep

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Perennial grasses will account for approximately 16 billion gallons of renewable fuels by the year 2022, contributing significantly to carbon and nitrogen sequestration. However, perennial grasses productivity can be limited by severe freezing conditions in some geographical areas, although these risks could decrease with the advance of climate warming, the possibility of unpredictable early cold events cannot be discarded. We conducted a study on the model perennial grass Brachypodium sylvaticum to investigate the molecular mechanisms that contribute to cold and freezing adaption. The study was performed on two different B. sylvaticum accessions, Ain1 and Osl1, typical to warm and cold climates, respectively. Both accessions were grown under controlled conditions with subsequent cold acclimation followed by freezing stress. For each treatment a set of morphological parameters, transcription, metabolite, and lipid profiles were measured. State-of-the-art algorithms were employed to analyze cross-component relationships. Phenotypic analysis revealed higher adaption of Osl1 to freezing stress. Our analysis highlighted the differential regulation of the TCA cycle and the GABA shunt between Ain1 and Osl1. Osl1 adapted to freezing stress by repressing the GABA shunt activity, avoiding the detrimental reduction in fatty acid biosynthesis and the concomitant detrimental effects on membrane integrity.The increase in energy demand coupled with the environmental impact of fossil fuels has led to the expansion of programs using perennial species as an alternative source of energy. In this context, perennial grasses, traditionally used as forage and turf, have become the preferred candidates for biomass cropping systems attributed to their ability to grow under low input conditions and high interception of sunlight 1 . Predictions showed that perennial grasses will account for approximately 16 billion gallons of renewable fuels by the year 2022 2,3 . Perennial grasses have shown to support carbon (C) and nitrogen (N) sequestration in the soil 4-6 , contributing to mitigate climate change and environmental degradation 7-9 . Brachypodium sylvaticum is a perennial grass with a simple genome, self-fertility, a short life cycle, and low growth requirements. Its recently released genome, expression gene atlas 10 and well established genetic transformation have made it an efficient model to study the genetic, molecular, and physiological components of perennial grasses 11,12 .Unfavorable winter conditions, including freezing, limit the geographical range of many important crops and reduce their productivity due to growth repression 13,14 . Low temperatures combined with high light intensity provoke the inhibition of the photosystem II and ROS production leading to oxidative stress 15 . In addition, ice formation in the apoplast induces both, cell membrane integrity stress and osmotic stress 16 . The plant's response to low temperatures involves extensive reprograming of gene expression via transcription factors 17 , resulting in co...

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Structure and Functional Diversity of GCN5-Related N-Acetyltransferases (GNAT)

Cited by 128 publications

References 216 publications

Insight into the 3D structure and substrate specificity of previously uncharacterized GNAT superfamily acetyltransferases from pathogenic bacteria

Insight into the 3D structure and substrate specificity of previously uncharacterized GNAT superfamily acetyltransferases from pathogenic bacteria

Alternative catalytic residues in the active site of Esco acetyltransferases

Correlation-based network analysis combined with machine learning techniques highlight the role of the GABA shunt in Brachypodium sylvaticum freezing tolerance

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