1f3w › Citations

Structural and functional linkages between subunit interfaces in mammalian pyruvate kinase.

Wooll JO, Friesen RH, White MA, Watowich SJ, Fox RO, Lee JC, Czerwinski EW
J Mol Biol 312 525-40 (2001)
Cited: 33 times
EuropePMC logo PMID: 11563914

Abstract

Mammalian pyruvate kinase (PK) is a four-domain enzyme that is active as a homo-tetramer. Tissue-specific isozymes of PK exhibit distinct levels of allosteric regulation. PK expressed in muscle tissue (M1-PK) shows hyperbolic steady-state kinetics, whereas PK expressed in kidney tissue (M2-PK) displays sigmoidal kinetics. Rabbit M1 and M2-PK are isozymes whose sequences differ in only 22 out of 530 residues per subunit, and these changes are localized in an inter-subunit interface. Previous studies have shown that a single amino acid mutation to M1-PK at either the Y (S402P) or Z (T340 M) subunit interface can confer a level of allosteric regulation that is intermediate to M1-PK and M2-PK. In an effort to elucidate the roles of the inter-subunit interaction in signal transmission and the functional/structural connectivity between these interfaces, the S402P mutant of M1-PK was crystallized and its structure resolved to 2.8 A. Although the overall S402P M1-PK structure is nearly identical with the wild-type structure within experimental error, significant differences in the conformation of the backbone are found at the site of mutation along the Y interface. In addition, there is a significant change along the Z interface, namely, a loss of an inter-subunit salt-bridge between Asp177 of domain B and Arg341 of domain A of the opposing subunit. Concurrent with the loss of the salt-bridge is an increase in the degree of rotational flexibility of domain B that constitutes the active site. Comparison of previous PK structures shows a correlation between an increase in this domain movement with the loss of the Asp177: Arg341 salt-bridge. These results identify the structural linkages between the Y and Z interfaces in regulating the interconversion of conformational states of rabbit M1-PK.

Reviews - 1f3w mentioned but not cited (1)

  1. Modulation of allostery of pyruvate kinase by shifting of an ensemble of microstates. Lee JC. Acta Biochim Biophys Sin (Shanghai) 40 663-669 (2008)

Articles - 1f3w mentioned but not cited (7)

  1. An integrated native mass spectrometry and top-down proteomics method that connects sequence to structure and function of macromolecular complexes. Li H, Nguyen HH, Ogorzalek Loo RR, Campuzano IDG, Loo JA. Nat Chem 10 139-148 (2018)
  2. Computational Insights into Compaction of Gas-Phase Protein and Protein Complex Ions in Native Ion Mobility-Mass Spectrometry. Rolland AD, Prell JS. Trends Analyt Chem 116 282-291 (2019)
  3. Determining biophysical protein stability in lysates by a fast proteolysis assay, FASTpp. Minde DP, Minde DP, Maurice MM, Rüdiger SG. PLoS One 7 e46147 (2012)
  4. A Molecular Dynamics Study of Allosteric Transitions in Leishmania mexicana Pyruvate Kinase. Naithani A, Taylor P, Erman B, Walkinshaw MD. Biophys J 109 1149-1156 (2015)
  5. First-Principles Collision Cross Section Measurements of Large Proteins and Protein Complexes. McCabe JW, Mallis CS, Kocurek KI, Poltash ML, Shirzadeh M, Hebert MJ, Fan L, Walker TE, Zheng X, Jiang T, Dong S, Lin CW, Laganowsky A, Russell DH. Anal Chem 92 11155-11163 (2020)
  6. Functional energetic landscape in the allosteric regulation of muscle pyruvate kinase. 2. Fluorescence study. Herman P, Lee JC. Biochemistry 48 9456-9465 (2009)
  7. Evolutionary plasticity in the allosteric regulator-binding site of pyruvate kinase isoform PykA from Pseudomonas aeruginosa. Abdelhamid Y, Brear P, Greenhalgh J, Chee X, Rahman T, Welch M. J Biol Chem 294 15505-15516 (2019)


Articles citing this publication (25)

  1. The ConSurf-HSSP database: the mapping of evolutionary conservation among homologs onto PDB structures. Glaser F, Rosenberg Y, Kessel A, Pupko T, Ben-Tal N. Proteins 58 610-617 (2005)
  2. Isotype-specific inhibitors of the glycolytic key regulator pyruvate kinase subtype M2 moderately decelerate tumor cell proliferation. Spoden GA, Mazurek S, Morandell D, Bacher N, Ausserlechner MJ, Jansen-Dürr P, Eigenbrodt E, Zwerschke W. Int J Cancer 123 312-321 (2008)
  3. The SUMO-E3 ligase PIAS3 targets pyruvate kinase M2. Spoden GA, Morandell D, Ehehalt D, Fiedler M, Jansen-Dürr P, Hermann M, Zwerschke W. J Cell Biochem 107 293-302 (2009)
  4. Cyclosporine A inhibits breast cancer cell growth by downregulating the expression of pyruvate kinase subtype M2. Jiang K, He B, Lai L, Chen Q, Liu Y, Guo Q, Wang Q. Int J Mol Med 30 302-308 (2012)
  5. Pyruvate kinase deficiency in France: a 3-year study reveals 27 new mutations. Pissard S, Max-Audit I, Skopinski L, Vasson A, Vivien P, Bimet C, Goossens M, Galacteros F, Wajcman H. Br J Haematol 133 683-689 (2006)
  6. Addressing the diagnostic gaps in pyruvate kinase deficiency: Consensus recommendations on the diagnosis of pyruvate kinase deficiency. Bianchi P, Fermo E, Glader B, Kanno H, Agarwal A, Barcellini W, Eber S, Hoyer JD, Kuter DJ, Maia TM, Mañu-Pereira MDM, Kalfa TA, Pissard S, Segovia JC, van Beers E, Gallagher PG, Rees DC, van Wijk R, with the endorsement of EuroBloodNet, the European Reference Network in Rare Hematological Diseases. Am J Hematol 94 149-161 (2019)
  7. Fifteen novel mutations in PKLR associated with pyruvate kinase (PK) deficiency: structural implications of amino acid substitutions in PK. van Wijk R, Huizinga EG, van Wesel AC, van Oirschot BA, Hadders MA, van Solinge WW. Hum Mutat 30 446-453 (2009)
  8. Isoform-specific interaction of pyruvate kinase with hepatitis C virus NS5B. Wu X, Zhou Y, Zhang K, Liu Q, Guo D. FEBS Lett 582 2155-2160 (2008)
  9. Identification of regions of rabbit muscle pyruvate kinase important for allosteric regulation by phenylalanine, detected by H/D exchange mass spectrometry. Prasannan CB, Villar MT, Artigues A, Fenton AW. Biochemistry 52 1998-2006 (2013)
  10. Differential behavior of missense mutations in the intersubunit contact domain of the human pyruvate kinase M2 isozyme. Akhtar K, Gupta V, Koul A, Alam N, Bhat R, Bamezai RN. J Biol Chem 284 11971-11981 (2009)
  11. Effects of metabolites on the structural dynamics of rabbit muscle pyruvate kinase. Yu S, Lee LL, Lee JC. Biophys Chem 103 1-11 (2003)
  12. Changes in small-angle X-ray scattering parameters observed upon binding of ligand to rabbit muscle pyruvate kinase are not correlated with allosteric transitions. Fenton AW, Williams R, Trewhella J. Biochemistry 49 7202-7209 (2010)
  13. Sulphate removal induces a major conformational change in Leishmania mexicana pyruvate kinase in the crystalline state. Tulloch LB, Morgan HP, Hannaert V, Michels PA, Fothergill-Gilmore LA, Walkinshaw MD. J Mol Biol 383 615-626 (2008)
  14. Distinguishing the chemical moiety of phosphoenolpyruvate that contributes to allostery in muscle pyruvate kinase. Urness JM, Clapp KM, Timmons JC, Bai X, Chandrasoma N, Buszek KR, Fenton AW. Biochemistry 52 1-3 (2013)
  15. Exploring the limits of the usefulness of mutagenesis in studies of allosteric mechanisms. Tang Q, Alontaga AY, Holyoak T, Fenton AW. Hum Mutat 38 1144-1154 (2017)
  16. `In crystallo' substrate binding triggers major domain movements and reveals magnesium as a co-activator of Trypanosoma brucei pyruvate kinase. Zhong W, Morgan HP, McNae IW, Michels PA, Fothergill-Gilmore LA, Walkinshaw MD. Acta Crystallogr D Biol Crystallogr 69 1768-1779 (2013)
  17. Functional energetic landscape in the allosteric regulation of muscle pyruvate kinase. 1. Calorimetric study. Herman P, Lee JC. Biochemistry 48 9448-9455 (2009)
  18. Rheostat functional outcomes occur when substitutions are introduced at nonconserved positions that diverge with speciation. Swint-Kruse L, Martin TA, Page BM, Wu T, Gerhart PM, Dougherty LL, Tang Q, Parente DJ, Mosier BR, Bantis LE, Fenton AW. Protein Sci 30 1833-1853 (2021)
  19. Molecular basis of pyruvate kinase deficiency among Tunisians: description of new mutations affecting coding and noncoding regions in the PKLR gene. Jaouani M, Manco L, Kalai M, Chaouch L, Douzi K, Silva A, Macedo S, Darragi I, Boudriga I, Chaouachi D, Fitouri Z, Van Wijk R, Ribeiro ML, Abbes S. Int J Lab Hematol 39 223-231 (2017)
  20. Robotically assisted titration coupled to ion mobility-mass spectrometry reveals the interface structures and analysis parameters critical for multiprotein topology mapping. Zhong Y, Feng J, Ruotolo BT. Anal Chem 85 11360-11368 (2013)
  21. The allosteric effect of fructose bisphosphate on muscle pyruvate kinase studied by infrared spectroscopy. Kumar S, Barth A. J Phys Chem B 115 11501-11505 (2011)
  22. Structure, Function and Regulation of a Second Pyruvate Kinase Isozyme in Pseudomonas aeruginosa. Abdelhamid Y, Wang M, Parkhill SL, Brear P, Chee X, Rahman T, Welch M. Front Microbiol 12 790742 (2021)
  23. Molecular characterization and expression of the equine M(1) and M(2)-pyruvate kinase gene. Echigoya Y, Sato T, Itou T, Endo H, Sakai T. Comp Biochem Physiol B Biochem Mol Biol 151 125-132 (2008)
  24. Divalent cations in human liver pyruvate kinase exemplify the combined effects of complex-equilibrium and allosteric regulation. Martin TA, Fenton AW. Sci Rep 13 10557 (2023)
  25. PYK-SubstitutionOME: an integrated database containing allosteric coupling, ligand affinity and mutational, structural, pathological, bioinformatic and computational information about pyruvate kinase isozymes. Swint-Kruse L, Dougherty LL, Page B, Wu T, O'Neil PT, Prasannan CB, Timmons C, Tang Q, Parente DJ, Sreenivasan S, Holyoak T, Fenton AW. Database (Oxford) 2023 baad030 (2023)


Quick links