3zr4 › Citations

Catalysis uncoupling in a glutamine amidotransferase bienzyme by unblocking the glutaminase active site.

List F, Vega MC, Razeto A, Häger MC, Sterner R, Wilmanns M
Chem Biol 19 1589-99 (2012)
Related entries: 1gpw, 1k9v, 2wjz

Cited: 24 times
EuropePMC logo PMID: 23261602

Abstract

Nitrogen is incorporated into various metabolites by multifunctional glutamine amidotransferases via reactive ammonia generated by glutaminase hydrolysis of glutamine. Although this process is generally tightly regulated by subsequent synthase activity, little is known about how the glutaminase is inhibited in the absence of an activating signal. Here, we use imidazoleglycerolphosphate synthase as a model to investigate the mechanism of glutaminase regulation. A structure of the bienzyme-glutamine complex reveals that the glutaminase active site is in a catalysis-competent conformation but the ammonia pathway toward the synthase active site is blocked. Mutation of two residues blocking the pathway leads to a complete uncoupling of the two reactions and to a 2800-fold amplification of glutaminase activity. Our data advance the understanding of coupling enzymatic activities in glutamine amidotransferases and raise hypotheses of the underlying molecular mechanism.

Articles - 3zr4 mentioned but not cited (6)

  1. Light Regulation of Enzyme Allostery through Photo-responsive Unnatural Amino Acids. Kneuttinger AC, Straub K, Bittner P, Simeth NA, Bruckmann A, Busch F, Rajendran C, Hupfeld E, Wysocki VH, Horinek D, König B, Merkl R, Sterner R. Cell Chem Biol 26 1501-1514.e9 (2019)
  2. First insights of peptidoglycan amidation in Gram-positive bacteria - the high-resolution crystal structure of Staphylococcus aureus glutamine amidotransferase GatD. Leisico F, V Vieira D, Figueiredo TA, Silva M, Cabrita EJ, Sobral RG, Ludovice AM, Trincão J, Romão MJ, de Lencastre H, Santos-Silva T. Sci Rep 8 5313 (2018)
  3. Time Evolution of the Millisecond Allosteric Activation of Imidazole Glycerol Phosphate Synthase. Calvó-Tusell C, Maria-Solano MA, Osuna S, Feixas F. J Am Chem Soc 144 7146-7159 (2022)
  4. The Role of Gene Elongation in the Evolution of Histidine Biosynthetic Genes. Del Duca S, Chioccioli S, Vassallo A, Castronovo LM, Fani R. Microorganisms 8 E732 (2020)
  5. Modeling Catalysis in Allosteric Enzymes: Capturing Conformational Consequences. Klem H, McCullagh M, Paton RS. Top Catal 65 165-186 (2022)
  6. Catalytic Effects of Active Site Conformational Change in the Allosteric Activation of Imidazole Glycerol Phosphate Synthase. Klem H, Alegre-Requena JV, Paton RS. ACS Catal 13 16249-16257 (2023)


Reviews citing this publication (4)

  1. Nitrogen assimilation in Escherichia coli: putting molecular data into a systems perspective. van Heeswijk WC, Westerhoff HV, Boogerd FC. Microbiol Mol Biol Rev 77 628-695 (2013)
  2. Allostery in enzyme catalysis. Lisi GP, Loria JP. Curr Opin Struct Biol 47 123-130 (2017)
  3. Emerging Roles of Protein Deamidation in Innate Immune Signaling. Zhao J, Li J, Xu S, Feng P. J Virol 90 4262-4268 (2016)
  4. GMP Synthetase: Allostery, Structure, and Function. Ballut L, Violot S, Kumar S, Aghajari N, Balaram H. Biomolecules 13 1379 (2023)

Articles citing this publication (14)

  1. Altering the allosteric pathway in IGPS suppresses millisecond motions and catalytic activity. Lisi GP, East KW, Batista VS, Loria JP. Proc Natl Acad Sci U S A 114 E3414-E3423 (2017)
  2. Dissecting Dynamic Allosteric Pathways Using Chemically Related Small-Molecule Activators. Lisi GP, Manley GA, Hendrickson H, Rivalta I, Batista VS, Loria JP. Structure 24 1155-1166 (2016)
  3. Structure of the essential peptidoglycan amidotransferase MurT/GatD complex from Streptococcus pneumoniae. Morlot C, Straume D, Peters K, Hegnar OA, Simon N, Villard AM, Contreras-Martel C, Leisico F, Breukink E, Gravier-Pelletier C, Le Corre L, Vollmer W, Pietrancosta N, Håvarstein LS, Zapun A. Nat Commun 9 3180 (2018)
  4. Active site coupling in Plasmodium falciparum GMP synthetase is triggered by domain rotation. Ballut L, Violot S, Shivakumaraswamy S, Thota LP, Sathya M, Kunala J, Dijkstra BW, Terreux R, Haser R, Balaram H, Aghajari N. Nat Commun 6 8930 (2015)
  5. Analysis of allosteric communication in a multienzyme complex by ancestral sequence reconstruction. Schupfner M, Straub K, Busch F, Merkl R, Sterner R. Proc Natl Acad Sci U S A 117 346-354 (2020)
  6. Molecular basis for the allosteric activation mechanism of the heterodimeric imidazole glycerol phosphate synthase complex. Wurm JP, Sung S, Kneuttinger AC, Hupfeld E, Sterner R, Wilmanns M, Sprangers R. Nat Commun 12 2748 (2021)
  7. Combining ancestral sequence reconstruction with protein design to identify an interface hotspot in a key metabolic enzyme complex. Holinski A, Heyn K, Merkl R, Sterner R. Proteins 85 312-321 (2017)
  8. Conformational changes involving ammonia tunnel formation and allosteric control in GMP synthetase. Oliver JC, Gudihal R, Burgner JW, Pedley AM, Zwierko AT, Davisson VJ, Linger RS. Arch Biochem Biophys 545 22-32 (2014)
  9. Role of allosteric switches and adaptor domains in long-distance cross-talk and transient tunnel formation. Sharma N, Ahalawat N, Sandhu P, Strauss E, Mondal J, Anand R. Sci Adv 6 eaay7919 (2020)
  10. Glutaminase 1 is a potential biomarker for chronic post-surgical pain in the rat dorsal spinal cord using differential proteomics. Wang H, Liu W, Cai Y, Ma L, Ma C, Luo A, Huang Y. Amino Acids 48 337-348 (2016)
  11. Importance of hydrophobic cavities in allosteric regulation of formylglycinamide synthetase: insight from xenon trapping and statistical coupling analysis. Tanwar AS, Goyal VD, Choudhary D, Panjikar S, Anand R. PLoS One 8 e77781 (2013)
  12. Artificial Light Regulation of an Allosteric Bienzyme Complex by a Photosensitive Ligand. Kneuttinger AC, Winter M, Simeth NA, Heyn K, Merkl R, König B, Sterner R. Chembiochem (2018)
  13. Letter Characterization of tunnel mutants reveals a catalytic step in ammonia delivery by an aminoacyl-tRNA amidotransferase. Zhao L, Rathnayake UM, Dewage SW, Wood WN, Veltri AJ, Cisneros GA, Hendrickson TL. FEBS Lett 590 3122-3132 (2016)
  14. Distinct allosteric pathways in imidazole glycerol phosphate synthase from yeast and bacteria. Maschietto F, Gheeraert A, Piazzi A, Batista VS, Rivalta I. Biophys J 121 119-130 (2022)


Related citations provided by authors (1)

  1. Structural evidence for ammonia tunneling across the (beta alpha)(8) barrel of the imidazole glycerol phosphate synthase bienzyme complex.. Douangamath A, Walker M, Beismann-Driemeyer S, Vega-Fernandez MC, Sterner R, Wilmanns M Structure 10 185-93 (2002)

Quick links