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Analysis of the structural determinants underlying discrimination between substrate and solvent in beta-phosphoglucomutase catalysis.

Dai J, Finci L, Zhang C, Lahiri S, Zhang G, Peisach E, Allen KN, Dunaway-Mariano D
Biochemistry 48 1984-95 (2009)
Related entries: 1o03, 1o08

Cited: 25 times
EuropePMC logo PMID: 19154134

Abstract

Tauhe beta-phosphoglucomutase (beta-PGM) of the haloacid dehalogenase enzyme superfamily (HADSF) catalyzes the conversion of beta-glucose 1-phosphate (betaG1P) to glucose 6-phosphate (G6P) using Asp8 of the core domain active site to mediate phosphoryl transfer from beta-glucose 1,6-(bis)phosphate (betaG1,6bisP) to betaG1P. Herein, we explore the mechanism by which hydrolysis of the beta-PGM phospho-Asp8 is avoided during the time that the active site must remain open to solvent to allow the exchange of the bound product G6P with the substrate betaG1P. On the basis of structural information, a model of catalysis is proposed in which the general acid/base (Asp10) side chain moves from a position where it forms a hydrogen bond to the Thr16-Ala17 portion of the domain-domain linker to a functional position where it forms a hydrogen bond to the substrate leaving group O and a His20-Lys76 pair of the cap domain. This repositioning of the general acid/base within the core domain active site is coordinated with substrate-induced closure of the cap domain over the core domain. The model predicts that Asp10 is required for general acid/base catalysis and for stabilization of the enzyme in the cap-closed conformation. It also predicts that hinge residue Thr16 plays a key role in productive domain-domain association, that hydrogen bond interaction with the Thr16 backbone amide NH group is required to prevent phospho-Asp8 hydrolysis in the cap-open conformation, and that the His20-Lys76 pair plays an important role in substrate-induced cap closure. The model is examined via kinetic analyses of Asp10, Thr16, His20, and Lys76 site-directed mutants. Replacement of Asp10 with Ala, Ser, Cys, Asn, or Glu resulted in no observable activity. The kinetic consequences of the replacement of linker residue Thr16 with Pro include a reduced rate of Asp8 phosphorylation by betaG1,6bisP, a reduced rate of cycling of the phosphorylated enzyme to convert betaG1P to G6P, and an enhanced rate of phosphoryl transfer from phospho-Asp8 to water. The X-ray crystal structure of the T16P mutant at 2.7 A resolution provides a snapshot of the enzyme in an unnatural cap-open conformation where the Asp10 side chain is located in the core domain active site. The His20 and Lys76 site-directed mutants exhibit reduced activity in catalysis of the Asp8-mediated phosphoryl transfer between betaG1,6bisP and betaG1P but no reduction in the rate of phospho-Asp8 hydrolysis. Taken together, the results support a substrate induced-fit model of catalysis in which betaG1P binding to the core domain facilitates recruitment of the general acid/base Asp10 to the catalytic site and induces cap closure.

Articles - 3fm9 mentioned but not cited (1)

  1. Analysis of the structural determinants underlying discrimination between substrate and solvent in beta-phosphoglucomutase catalysis. Dai J, Finci L, Zhang C, Lahiri S, Zhang G, Peisach E, Allen KN, Dunaway-Mariano D. Biochemistry 48 1984-1995 (2009)


Reviews citing this publication (4)

  1. Enzyme promiscuity: engine of evolutionary innovation. Pandya C, Farelli JD, Dunaway-Mariano D, Allen KN. J Biol Chem 289 30229-30236 (2014)
  2. Markers of fitness in a successful enzyme superfamily. Allen KN, Dunaway-Mariano D. Curr Opin Struct Biol 19 658-665 (2009)
  3. Metal Fluorides: Tools for Structural and Computational Analysis of Phosphoryl Transfer Enzymes. Jin Y, Molt RW, Blackburn GM. Top Curr Chem (Cham) 375 36 (2017)
  4. Catalytic scaffolds for phosphoryl group transfer. Allen KN, Dunaway-Mariano D. Curr Opin Struct Biol 41 172-179 (2016)

Articles citing this publication (20)

  1. Panoramic view of a superfamily of phosphatases through substrate profiling. Huang H, Pandya C, Liu C, Al-Obaidi NF, Wang M, Zheng L, Toews Keating S, Aono M, Love JD, Evans B, Seidel RD, Hillerich BS, Garforth SJ, Almo SC, Mariano PS, Dunaway-Mariano D, Allen KN, Farelli JD. Proc Natl Acad Sci U S A 112 E1974-83 (2015)
  2. Atomic details of near-transition state conformers for enzyme phosphoryl transfer revealed by MgF-3 rather than by phosphoranes. Baxter NJ, Bowler MW, Alizadeh T, Cliff MJ, Hounslow AM, Wu B, Berkowitz DB, Williams NH, Blackburn GM, Waltho JP. Proc Natl Acad Sci U S A 107 4555-4560 (2010)
  3. Cooperative Electrostatic Interactions Drive Functional Evolution in the Alkaline Phosphatase Superfamily. Barrozo A, Duarte F, Bauer P, Carvalho AT, Kamerlin SC. J Am Chem Soc 137 9061-9076 (2015)
  4. Near attack conformers dominate β-phosphoglucomutase complexes where geometry and charge distribution reflect those of substrate. Griffin JL, Bowler MW, Baxter NJ, Leigh KN, Dannatt HR, Hounslow AM, Blackburn GM, Webster CE, Cliff MJ, Waltho JP. Proc Natl Acad Sci U S A 109 6910-6915 (2012)
  5. Divergence of structure and function in the haloacid dehalogenase enzyme superfamily: Bacteroides thetaiotaomicron BT2127 is an inorganic pyrophosphatase. Huang H, Patskovsky Y, Toro R, Farelli JD, Pandya C, Almo SC, Allen KN, Dunaway-Mariano D. Biochemistry 50 8937-8949 (2011)
  6. Structural determinants of substrate recognition in the HAD superfamily member D-glycero-D-manno-heptose-1,7-bisphosphate phosphatase (GmhB) . Nguyen HH, Wang L, Huang H, Peisach E, Dunaway-Mariano D, Allen KN. Biochemistry 49 1082-1092 (2010)
  7. Probing Mechanistic Similarities between Response Regulator Signaling Proteins and Haloacid Dehalogenase Phosphatases. Immormino RM, Starbird CA, Silversmith RE, Bourret RB. Biochemistry 54 3514-3527 (2015)
  8. Identification and characterization of an archaeal kojibiose catabolic pathway in the hyperthermophilic Pyrococcus sp. strain ST04. Jung JH, Seo DH, Holden JF, Park CS. J Bacteriol 196 1122-1131 (2014)
  9. Computer simulations of the catalytic mechanism of wild-type and mutant β-phosphoglucomutase. Barrozo A, Liao Q, Esguerra M, Marloie G, Florián J, Williams NH, Kamerlin SCL. Org Biomol Chem 16 2060-2073 (2018)
  10. Mechanism of Substrate Recognition and Catalysis of the Haloalkanoic Acid Dehalogenase Family Member α-Phosphoglucomutase. Zhang C, Allen KN, Dunaway-Mariano D. Biochemistry 57 4504-4517 (2018)
  11. The X-ray crystallographic structure and specificity profile of HAD superfamily phosphohydrolase BT1666: comparison of paralogous functions in B. thetaiotaomicron. Lu Z, Dunaway-Mariano D, Allen KN. Proteins 79 3099-3107 (2011)
  12. Structural Basis of the Molecular Switch between Phosphatase and Mutase Functions of Human Phosphomannomutase 1 under Ischemic Conditions. Ji T, Zhang C, Zheng L, Dunaway-Mariano D, Allen KN. Biochemistry 57 3480-3492 (2018)
  13. Theoretical investigation of the enzymatic phosphoryl transfer of β-phosphoglucomutase: revisiting both steps of the catalytic cycle. Elsässer B, Dohmeier-Fischer S, Fels G. J Mol Model 18 3169-3179 (2012)
  14. Unexpected Evolution of Lesion-Recognition Modules in Eukaryotic NER and Kinetoplast DNA Dynamics Proteins from Bacterial Mobile Elements. Krishnan A, Burroughs AM, Iyer LM, Aravind L. iScience 9 192-208 (2018)
  15. 1H, 15N and 13C backbone resonance assignments of the P146A variant of β-phosphoglucomutase from Lactococcus lactis in its substrate-free form. Cruz-Navarrete FA, Baxter NJ, Wood HP, Hounslow AM, Waltho JP. Biomol NMR Assign 13 349-356 (2019)
  16. Allomorphy as a mechanism of post-translational control of enzyme activity. Wood HP, Cruz-Navarrete FA, Baxter NJ, Trevitt CR, Robertson AJ, Dix SR, Hounslow AM, Cliff MJ, Waltho JP. Nat Commun 11 5538 (2020)
  17. An Enzyme with High Catalytic Proficiency Utilizes Distal Site Substrate Binding Energy to Stabilize the Closed State but at the Expense of Substrate Inhibition. Robertson AJ, Cruz-Navarrete FA, Wood HP, Vekaria N, Hounslow AM, Bisson C, Cliff MJ, Baxter NJ, Waltho JP. ACS Catal 12 3149-3164 (2022)
  18. Structural Analysis of Binding Determinants of Salmonella typhimurium Trehalose-6-phosphate Phosphatase Using Ground-State Complexes. Harvey CM, O'Toole KH, Liu C, Mariano P, Dunaway-Mariano D, Allen KN. Biochemistry 59 3247-3257 (2020)
  19. Observing enzyme ternary transition state analogue complexes by 19F NMR spectroscopy. Ampaw A, Carroll M, von Velsen J, Bhattasali D, Cohen A, Bowler MW, Jakeman DL. Chem Sci 8 8427-8434 (2017)
  20. The conserved crown bridge loop at the catalytic centre of enzymes of the haloacid dehalogenase superfamily. Leader DP, Milner-White EJ. Curr Res Struct Biol 6 100105 (2023)


Related citations provided by authors (1)

  1. The pentacovalent phosphorus intermediate of a phosphoryl transfer reaction.. Lahiri SD, Zhang G, Dunaway-Mariano D, Allen KN Science 299 2067-71 (2003)

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