Abstract
Triosephosphate isomerase (TIM) is a perfectly evolved enzyme which very fast interconverts dihydroxyacetone phosphate and d-glyceraldehyde-3-phosphate. Its catalytic site is at the dimer interface, but the four catalytic residues, Asn11, Lys13, His95 and Glu167, are from the same subunit. Glu167 is the catalytic base. An important feature of the TIM active site is the concerted closure of loop-6 and loop-7 on ligand binding, shielding the catalytic site from bulk solvent. The buried active site stabilises the enediolate intermediate. The catalytic residue Glu167 is at the beginning of loop-6. On closure of loop-6, the Glu167 carboxylate moiety moves approximately 2 Å to the substrate. The dynamic properties of the Glu167 side chain in the enzyme substrate complex are a key feature of the proton shuttling mechanism. Two proton shuttling mechanisms, the classical and the criss-cross mechanism, are responsible for the interconversion of the substrates of this enolising enzyme.
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Abbreviations
- BHAP:
-
Bromohydroxyacetone phosphate
- d-GAP:
-
d-Glyceraldehyde-3-phosphate
- DHAP:
-
Dihydroxyacetone phosphate
- d,l-GOP:
-
d,l-Glycidolphosphate
- IPP:
-
2-(N-formyl-N-hydroxy)-amino-ethylphosphonate
- PGH:
-
Phosphoglycolohydroxamate
- PGI:
-
Phosphoglucose isomerase
- RPI:
-
d-Ribose-5-phosphate isomerase
- TIM:
-
Triosephosphate isomerase
- 2PG:
-
2-Phosphoglycollate
References
Knowles JR, Albery WJ (1977) Perfection in enzyme catalysis: the energetics of triosephosphate isomerase. Acc Chem Res 10:105–111
Knowles JR (1991) Enzyme catalysis: not different, just better. Nature 350:121–124
Harris TK (2008) The mechanistic ventures of triosephosphate isomerase. IUBMB Life 60:195–198
Cui Q, Karplus M (2003) Catalysis and specificity in enzymes: a study of triosephosphate isomerase and comparison with methyl glyoxal synthase. Adv Protein Chem 66:315–372
Albery WJ, Knowles JR (1977) Efficiency and evolution of enzyme catalysis. Angew Chem Int Ed Engl 16:285–293
Fersht AR (1999) Structure and mechanism in protein science. Freeman, New York
Rose IA (1962) Mechanism of C–H bond cleavage in aldolase and isomerase reactions. Brookhaven Symp Biol 15:293–309
Richard JP (1984) Acid–base catalysis of the elimination and isomerization reactions of triose phosphates. J Am Chem Soc 106:4926–4936
Wolfenden R (1969) Transition state analogues for enzyme catalysis. Nature 223:704–705
Banner DW, Bloomer AC, Petsko GA, Phillips DC, Pogson CI, Wilson IA, Corran PH, Furth AJ, Milman JD, Offord RE, Priddle JD, Waley SG (1975) Structure of chicken muscle triose phosphate isomerase determined crystallographically at 2.5 angstrom resolution using amino acid sequence data. Nature 255:609–614
Lambeir AM, Opperdoes FR, Wierenga RK (1987) Kinetic properties of triose-phosphate isomerase from Trypanosoma brucei brucei. A comparison with the rabbit muscle and yeast enzymes. Eur J Biochem 168:69–74
Rose IA, O’Connell EL (1969) Inactivation and labeling of triose phosphate isomerase and enolase by glycidol phosphate. J Biol Chem 244:6548–6550
De la Mare S, Coulson AF, Knowles JR, Priddle JD, Offord RE (1972) Active-site labelling of triose phosphate isomerase. The reaction of bromohydroxyacetone phosphate with a unique glutamic acid residue and the migration of the label to tyrosine. Biochem J 129:321–331
Hartman FC (1971) Haloacetol phosphates. Characterization of the active site of rabbit muscle triose phosphate isomerase. Biochemistry 10:146–154
Schray KJ, O’Connell EL, Rose IA (1973) Inactivation of muscle triose phosphate isomerase by d- and l-glycidol phosphate. J Biol Chem 248:2214–2218
Wolfenden R, Snider MJ (2001) The depth of chemical time and the power of enzymes as catalysts. Acc Chem Res 34:938–945
Hall A, Knowles JR (1975) The uncatalyzed rates of enolization of dihydroxyacetone phosphate and of glyceraldehyde 3-phosphate in neutral aqueous solution. The quantitative assessment of the effectiveness of an enzyme catalyst. Biochemistry 14:4348–4353
Kursula I, Partanen S, Lambeir AM, Antonov DM, Augustyns K, Wierenga RK (2001) Structural determinants for ligand binding and catalysis of triosephosphate isomerase. Eur J Biochem 268:5189–5196
Jogl G, Rozovsky S, McDermott AE, Tong L (2003) Optimal alignment for enzymatic proton transfer: structure of the Michaelis complex of triosephosphate isomerase at 1.2-A resolution. Proc Natl Acad Sci USA 100:50–55
Alahuhta M, Wierenga RK (2010) Atomic resolution crystallography of a complex of triosephosphate isomerase with a reaction-intermediate analog: new insight in the proton transfer reaction mechanism. Proteins 78:1878–1888
Lesk AM, Branden CI, Chothia C (1989) Structural principles of alpha/beta barrel proteins: the packing of the interior of the sheet. Proteins 5:139–148
Copley RR, Bork P (2000) Homology among (betaalpha)(8) barrels: implications for the evolution of metabolic pathways. J Mol Biol 303:627–641
Nagano N, Orengo CA, Thornton JM (2002) One fold with many functions: the evolutionary relationships between TIM barrel families based on their sequences, structures and functions. J Mol Biol 321:741–765
Wierenga RK (2001) The TIM-barrel fold: a versatile framework for efficient enzymes. FEBS Lett 492:193–198
Pujadas G, Palau J (2001) Evolution of alpha-amylases: architectural features and key residues in the stabilization of the (beta/alpha)(8) scaffold. Mol Biol Evol 18:38–54
Go MK, Koudelka A, Amyes TL, Richard JP (2010) The role of Lys-12 in catalysis by triosephosphate isomerase: a two-part substrate approach. Biochemistry 49:5377–5389
Lolis E, Petsko GA (1990) Transition-state analogues in protein crystallography: probes of the structural source of enzyme catalysis. Annu Rev Biochem 59:597–630
Webb MR, Knowles JR (1975) The orientation and accessibility of substrates on the active site of triosephosphate isomerase. Biochemistry 14:4692–4698
Lolis E, Petsko GA (1990) Crystallographic analysis of the complex between triosephosphate isomerase and 2-phosphoglycolate at 2.5-A resolution: implications for catalysis. Biochemistry 29:6619–6625
Collins KD (1974) An activated intermediate analogue. The use of phosphoglycolohydroxamate as a stable analogue of a transiently occurring dihydroxyacetone phosphate-derived enolate in enzymatic catalysis. J Biol Chem 249:136–142
Davenport RC, Bash PA, Seaton BA, Karplus M, Petsko GA, Ringe D (1991) Structure of the triosephosphate isomerase-phosphoglycolohydroxamate complex: an analogue of the intermediate on the reaction pathway. Biochemistry 30:5821–5826
Zhang Z, Sugio S, Komives EA, Liu KD, Knowles JR, Petsko GA, Ringe D (1994) Crystal structure of recombinant chicken triosephosphate isomerase-phosphoglycolohydroxamate complex at 1.8-A resolution. Biochemistry 33:2830–2837
Schliebs W, Thanki N, Eritja R, Wierenga R (1996) Active site properties of monomeric triosephosphate isomerase (monoTIM) as deduced from mutational and structural studies. Protein Sci 5:229–239
Fonvielle M, Mariano S, Therisod M (2005) New inhibitors of rabbit muscle triose-phosphate isomerase. Bioorg Med Chem Lett 15:2906–2909
Campbell ID, Jones RB, Kiener PA, Waley SG (1979) Enzyme-substrate and enzyme-inhibitor complexes of triose phosphate isomerase studied by 31P nuclear magnetic resonance. Biochem J 179:607–621
Orosz F, Olah J, Ovadi J (2006) Triosephosphate isomerase deficiency: facts and doubts. IUBMB Life 58:703–715
Helfert S, Estevez AM, Bakker B, Michels P, Clayton C (2001) Roles of triosephosphate isomerase and aerobic metabolism in Trypanosoma brucei. Biochem J 357:117–125
Michels PA (1986) Evolutionary aspects of trypanosomes: analysis of genes. J Mol Evol 24:45–52
Orosz F, Olah J, Ovadi J (2009) Triosephosphate isomerase deficiency: new insights into an enigmatic disease. Biochim Biophys Acta 1792:1168–1174
Richard JP (2008) Restoring a metabolic pathway. ACS Chem Biol 3:605–607
Rodriguez-Almazan C, Arreola R, Rodriguez-Larrea D, Aguirre-Lopez B, de Gomez-Puyou MT, Perez-Montfort R, Costas M, Gomez-Puyou A, Torres-Larios A (2008) Structural basis of human triosephosphate isomerase deficiency: mutation E104D is related to alterations of a conserved water network at the dimer interface. J Biol Chem 283:23254–23263
Schneider A, Westwood B, Yim C, Cohen-Solal M, Rosa R, Labotka R, Eber S, Wolf R, Lammi A, Beutler E (1996) The 1591C mutation in triosephosphate isomerase (TPI) deficiency. Tightly linked polymorphisms and a common haplotype in all known families. Blood Cells Mol Dis 22:115–125
Maes D, Zeelen JP, Thanki N, Beaucamp N, Alvarez M, Thi MH, Backmann J, Martial JA (1999) The crystal structure of triosephosphate isomerase (TIM) from Thermotoga maritima: a comparative thermostability structural analysis of ten different TIM structures. Proteins 37:441–453
Schneider AS (2000) Triosephosphate isomerase deficiency: historical perspectives and molecular aspects. Baillieres Best Pract Res Clin Haematol 13:119–140
Daar IO, Artymiuk PJ, Phillips DC, Maquat LE (1986) Human triose-phosphate isomerase deficiency: a single amino acid substitution results in a thermolabile enzyme. Proc Natl Acad Sci USA 83:7903–7907
Guix FX, Ill-Raga G, Bravo R, Nakaya T, de Fabritiis G, Coma M, Miscione GP, Villà-Freixa J, Suzuki T, Fernàndez-Busquets X, Valverde MA, de Strooper B, Muñoz FJ (2009) Amyloid-dependent triosephosphate isomerase nitrotyrosination induces glycation and tau fibrillation. Brain 132:1335–1345
Rozovsky S, McDermott AE (2007) Substrate product equilibrium on a reversible enzyme, triosephosphate isomerase. Proc Natl Acad Sci USA 104:2080–2085
Albery WJ, Knowles JR (1976) Free-energy profile of the reaction catalyzed by triosephosphate isomerase. Biochemistry 15:5627–5631
Albery WJ, Knowles JR (1976) Evolution of enzyme function and the development of catalytic efficiency. Biochemistry 15:5631–5640
Blacklow SC, Raines RT, Lim WA, Zamore PD, Knowles JR (1988) Triosephosphate isomerase catalysis is diffusion controlled. Appendix: analysis of triose phosphate equilibria in aqueous solution by 31P NMR. Biochemistry 27:1158–1167
Desamero R, Rozovsky S, Zhadin N, McDermott A, Callender R (2003) Active site loop motion in triosephosphate isomerase: T-jump relaxation spectroscopy of thermal activation. Biochemistry 42:2941–2951
Cui Q, Karplus M (2001) Triosephosphate isomerase: a theoretical comparison of alternative pathways. J Am Chem Soc 123:2284–2290
Guallar V, Jacobson M, McDermott A, Friesner RA (2004) Computational modeling of the catalytic reaction in triosephosphate isomerase. J Mol Biol 337:227–239
Feierberg I, Åquist J (2002) Computational modeling of enzymatic keto-enol isomerization reactions. Theor Chem Acc 108:71–84
Thakur SS, Deepalakshmi PD, Gayathri P, Banerjee M, Murthy MR, Balaram P (2009) Detection of the protein dimers, multiple monomeric states and hydrated forms of Plasmodium falciparum triosephosphate isomerase in the gas phase. Protein Eng Des Sel 22:289–304
Belasco JG, Herlihy JM, Knowles JR (1978) Critical ionization states in the reaction catalyzed by triosephosphate isomerase. Biochemistry 17:2971–2978
Pompliano DL, Peyman A, Knowles JR (1990) Stabilization of a reaction intermediate as a catalytic device: definition of the functional role of the flexible loop in triosephosphate isomerase. Biochemistry 29:3186–3194
Lodi PJ, Chang LC, Knowles JR, Komives EA (1994) Triosephosphate isomerase requires a positively charged active site: the role of lysine-12. Biochemistry 33:2809–2814
Belasco JG, Knowles JR (1980) Direct observation of substrate distortion by triosephosphate isomerase using Fourier transform infrared spectroscopy. Biochemistry 19:472–477
Zhang Z, Komives EA, Sugio S, Blacklow SC, Narayana N, Xuong NH, Stock AM, Petsko GA, Ringe D (1999) The role of water in the catalytic efficiency of triosephosphate isomerase. Biochemistry 38:4389–4397
Gayathri P, Banerjee M, Vijayalakshmi A, Balaram H, Balaram P, Murthy MR (2009) Biochemical and structural characterization of residue 96 mutants of Plasmodium falciparum triosephosphate isomerase: active-site loop conformation, hydration and identification of a dimer-interface ligand-binding site. Acta Crystallogr D Biol Crystallogr 65:847–857
Kursula I, Wierenga RK (2003) Crystal structure of triosephosphate isomerase complexed with 2-phosphoglycolate at 0.83-A resolution. J Biol Chem 278:9544–9551
Donnini S, Groenhof G, Wierenga RK, Juffer AH (2006) The planar conformation of a strained proline ring: a QM/MM study. Proteins 64:700–710
Allen SC, Muirhead H (1996) Refined three-dimensional structure of cat-muscle (M1) pyruvate kinase at a resolution of 2.6 A. Acta Crystallogr D Biol Crystallogr 52:499–504
Raychaudhuri S, Younas F, Karplus PA, Faerman CH, Ripoll DR (1997) Backbone makes a significant contribution to the electrostatics of alpha/beta-barrel proteins. Protein Sci 6:1849–1857
Livesay DR, La D (2005) The evolutionary origins and catalytic importance of conserved electrostatic networks within TIM-barrel proteins. Protein Sci 14:1158–1170
Henn-Sax M, Hocker B, Wilmanns M, Sterner R (2001) Divergent evolution of (betaalpha)8-barrel enzymes. Biol Chem 382:1315–1320
Hocker B, Lochner A, Seitz T, Claren J, Sterner R (2009) High-resolution crystal structure of an artificial (betaalpha)(8)-barrel protein designed from identical half-barrels. Biochemistry 48:1145–1147
Hocker B (2005) Directed evolution of (betaalpha)(8)-barrel enzymes. Biomol Eng 22:31–38
Sterner R, Hocker B (2005) Catalytic versatility, stability, and evolution of the (betaalpha)8-barrel enzyme fold. Chem Rev 105:4038–4055
Claren J, Malisi C, Hocker B, Sterner R (2009) Establishing wild-type levels of catalytic activity on natural and artificial (beta alpha)8-barrel protein scaffolds. Proc Natl Acad Sci USA 106:3704–3709
Rothlisberger D, Khersonsky O, Wollacott AM, Jiang L, DeChancie J, Betker J, Gallaher JL, Althoff EA, Zanghellini A, Dym O, Albeck S, Houk KN, Tawfik DS, Baker D (2008) Kemp elimination catalysts by computational enzyme design. Nature 453:190–195
Singh SK, Maithal K, Balaram H, Balaram P (2001) Synthetic peptides as inactivators of multimeric enzymes: inhibition of Plasmodium falciparum triosephosphate isomerase by interface peptides. FEBS Lett 501:19–23
Tellez-Valencia A, Olivares-Illana V, Hernandez-Santoyo A, Perez-Montfort R, Costas M, Rodriguez-Romero A, López-Calahorra F, Tuena De Gómez-Puyou M, Gómez-Puyou A (2004) Inactivation of triosephosphate isomerase from Trypanosoma cruzi by an agent that perturbs its dimer interface. J Mol Biol 341:1355–1365
Olivares-Illana V, Rodriguez-Romero A, Becker I, Berzunza M, Garcia J, Perez-Montfort R, Cabrera N, López-Calahorra F, de Gómez-Puyou MT, Gómez-Puyou A (2007) Perturbation of the dimer interface of triosephosphate isomerase and its effect on Trypanosoma cruzi. PLoS Negl Trop Dis 1:e1
Borchert TV, Abagyan R, Kishan KV, Zeelen JP, Wierenga RK (1993) The crystal structure of an engineered monomeric triosephosphate isomerase, monoTIM: the correct modelling of an eight-residue loop. Structure 1:205–213
Borchert TV, Abagyan R, Jaenicke R, Wierenga RK (1994) Design, creation, and characterization of a stable, monomeric triosephosphate isomerase. Proc Natl Acad Sci USA 91:1515–1518
Borchert TV, Kishan KV, Zeelen JP, Schliebs W, Thanki N, Abagyan R, Jaenicke R, Wierenga RK (1995) Three new crystal structures of point mutation variants of monoTIM: conformational flexibility of loop-1, loop-4 and loop-8. Structure 3:669–679
Norledge BV, Lambeir AM, Abagyan RA, Rottmann A, Fernandez AM, Filimonov VV, Peter MG, Wierenga RK (2001) Modeling, mutagenesis, and structural studies on the fully conserved phosphate-binding loop (loop 8) of triosephosphate isomerase: toward a new substrate specificity. Proteins 42:383–389
Lambeir AM, Backmann J, Ruiz-Sanz J, Filimonov V, Nielsen JE, Kursula I, Norledge BV, Wierenga RK (2000) The ionization of a buried glutamic acid is thermodynamically linked to the stability of Leishmania mexicana triose phosphate isomerase. Eur J Biochem 267:2516–2524
Saab-Rincon G, Juarez VR, Osuna J, Sanchez F, Soberon X (2001) Different strategies to recover the activity of monomeric triosephosphate isomerase by directed evolution. Protein Eng 14:149–155
Thanki N, Zeelen JP, Mathieu M, Jaenicke R, Abagyan RA, Wierenga RK, Schliebs W (1997) Protein engineering with monomeric triosephosphate isomerase (monoTIM): the modelling and structure verification of a seven-residue loop. Protein Eng 10:159–167
Alahuhta M, Salin M, Casteleijn MG, Kemmer C, El-Sayed I, Augustyns K, Neubauer P, Wierenga RK (2008) Structure-based protein engineering efforts with a monomeric TIM variant: the importance of a single point mutation for generating an active site with suitable binding properties. Protein Eng Des Sel 21:257–266
Kursula I, Salin M, Sun J, Norledge BV, Haapalainen AM, Sampson NS, Wierenga RK (2004) Understanding protein lids: structural analysis of active hinge mutants in triosephosphate isomerase. Protein Eng Des Sel 17:375–382
Williams JC, Zeelen JP, Neubauer G, Vriend G, Backmann J, Michels PA, Lambeir AM, Wierenga RK (1999) Structural and mutagenesis studies of leishmania triosephosphate isomerase: a point mutation can convert a mesophilic enzyme into a superstable enzyme without losing catalytic power. Protein Eng 12:243–250
Nagorski RW, Richard JP (2001) Mechanistic imperatives for aldose-ketose isomerization in water: specific, general base- and metal ion-catalyzed isomerization of glyceraldehyde with proton and hydride transfer. J Am Chem Soc 123:794–802
Gerlt JA, Gassman PG (1993) Understanding the rates of certain enzyme-catalyzed reactions: proton abstraction from carbon acids, acyl-transfer reactions, and displacement reactions of phosphodiesters. Biochemistry 32:11943–11952
Frey PA, Hegeman AD (2007) Enzymatic reaction mechanisms. Oxford University Press, New York
Pihko P, Rapakko S, Wierenga RK (2009) Oxyanion holes and their mimics. In: Pihko P (ed) Hydrogen bonding in organic synthesis. Wiley, Weinheim, pp 43–71
Rose IA (1975) Mechanism of the aldose-ketose isomerase reactions. Adv Enzymol Relat Areas Mol Biol 43:491–517
Roos AK, Burgos E, Ericsson DJ, Salmon L, Mowbray SL (2005) Competitive inhibitors of Mycobacterium tuberculosis ribose-5-phosphate isomerase B reveal new information about the reaction mechanism. J Biol Chem 280:6416–6422
Arsenieva D, Hardre R, Salmon L, Jeffery CJ (2002) The crystal structure of rabbit phosphoglucose isomerase complexed with 5-phospho-d-arabinonohydroxamic acid. Proc Natl Acad Sci USA 99:5872–5877
Zhang R, Andersson CE, Savchenko A, Skarina T, Evdokimova E, Beasley S, Arrowsmith CH, Edwards AM, Joachimiak A, Mowbray SL (2003) Structure of Escherichia coli ribose-5-phosphate isomerase: a ubiquitous enzyme of the pentose phosphate pathway and the Calvin cycle. Structure 11:31–42
Hamada K, Ago H, Sugahara M, Nodake Y, Kuramitsu S, Miyano M (2003) Oxyanion hole-stabilized stereospecific isomerization in ribose-5-phosphate isomerase (Rpi). J Biol Chem 278:49183–49190
Arsenieva D, Jeffery CJ (2002) Conformational changes in phosphoglucose isomerase induced by ligand binding. J Mol Biol 323:77–84
Fenn TD, Ringe D, Petsko GA (2004) Xylose isomerase in substrate and inhibitor michaelis states: atomic resolution studies of a metal-mediated hydride shift. Biochemistry 43:6464–6474
Amyes TL, O’Donoghue AC, Richard JP (2001) Contribution of phosphate intrinsic binding energy to the enzymatic rate acceleration for triosephosphate isomerase. J Am Chem Soc 123:11325–11326
Morrow JR, Amyes TL, Richard JP (2008) Phosphate binding energy and catalysis by small and large molecules. Acc Chem Res 41:539–548
Amyes TL, Richard JP (2007) Enzymatic catalysis of proton transfer at carbon: activation of triosephosphate isomerase by phosphite dianion. Biochemistry 46:5841–5854
Go MK, Amyes TL, Richard JP (2009) Hydron transfer catalyzed by triosephosphate isomerase. Products of the direct and phosphite-activated isomerization of [1-(13)C]-glycolaldehyde in D(2)O. Biochemistry 48:5769–5778
Corey EJ, Sneen RA (1956) Stereoelectronic control in enolization-ketonization reactions. J Am Chem Soc 78:6269–6278
Richard JP, Amyes TL (2001) Proton transfer at carbon. Curr Opin Chem Biol 5:626–633
Silverman RB (2002) The organic chemistry of enzyme catalyzed reactions (revised edition). Academic Press, London
Hartman FC, LaMuraglia GM, Tomozawa Y, Wolfenden R (1975) The influence of pH on the interaction of inhibitors with triosephosphate isomerase and determination of the pKa of the active-site carboxyl group. Biochemistry 14:5274–5279
Alston WC 2nd, Kanska M, Murray CJ (1996) Secondary H/T and D/T isotope effects in enzymatic enolization reactions. Coupled motion and tunneling in the triosephosphate isomerase reaction. Biochemistry 35:12873–12881
Cleland WW, Frey PA, Gerlt JA (1998) The low barrier hydrogen bond in enzymatic catalysis. J Biol Chem 273:25529–25532
Harris TK, Abeygunawardana C, Mildvan AS (1997) NMR studies of the role of hydrogen bonding in the mechanism of triosephosphate isomerase. Biochemistry 36:14661–14675
Bash PA, Field MJ, Davenport RC, Petsko GA, Ringe D, Karplus M (1991) Computer simulation and analysis of the reaction pathway of triosephosphate isomerase. Biochemistry 30:5826–5832
Nickbarg EB, Davenport RC, Petsko GA, Knowles JR (1988) Triosephosphate isomerase: removal of a putatively electrophilic histidine residue results in a subtle change in catalytic mechanism. Biochemistry 27:5948–5960
Harris TK, Cole RN, Comer FI, Mildvan AS (1998) Proton transfer in the mechanism of triosephosphate isomerase. Biochemistry 37:16828–16838
Schramm VL (2007) Enzymatic transition state theory and transition state analogue design. J Biol Chem 282:28297–28300
Lodi PJ, Knowles JR (1991) Neutral imidazole is the electrophile in the reaction catalyzed by triosephosphate isomerase: structural origins and catalytic implications. Biochemistry 30:6948–6956
Gandour RD (1981) On the importance of orientation in general base catalysis by carboxylate. Bioorg Chem 10:169–176
O’Donoghue AC, Amyes TL, Richard JP (2005) Hydron transfer catalyzed by triosephosphate isomerase. Products of isomerization of dihydroxyacetone phosphate in D2O. Biochemistry 44:2622–2631
Herlihy JM, Maister SG, Albery WJ, Knowles JR (1976) Energetics of triosephosphate isomerase: the fate of the 1(R)-3H label of tritiated dihydroxyacetone phosphate in the isomerase reaction. Biochemistry 15:5601–5607
Rose IA, Fung WJ, Warms JV (1990) Proton diffusion in the active site of triosephosphate isomerase. Biochemistry 29:4312–4317
Aparicio R, Ferreira ST, Polikarpov I (2003) Closed conformation of the active site loop of rabbit muscle triosephosphate isomerase in the absence of substrate: evidence of conformational heterogeneity. J Mol Biol 334:1023–1041
Verlinde CL, Witmans CJ, Pijning T, Kalk KH, Hol WG, Callens M, Opperdoes FR (1992) Structure of the complex between trypanosomal triosephosphate isomerase and N-hydroxy-4-phosphono-butanamide: binding at the active site despite an “open” flexible loop conformation. Protein Sci 1:1578–1584
Parthasarathy S, Ravindra G, Balaram H, Balaram P, Murthy MR (2002) Structure of the Plasmodium falciparum triosephosphate isomerase-phosphoglycolate complex in two crystal forms: characterization of catalytic loop open and closed conformations in the ligand-bound state. Biochemistry 41:13178–13188
Noble ME, Zeelen JP, Wierenga RK (1993) Structures of the “open” and “closed” state of trypanosomal triosephosphate isomerase, as observed in a new crystal form: implications for the reaction mechanism. Proteins 16:311–326
Joseph D, Petsko GA, Karplus M (1990) Anatomy of a conformational change: hinged “lid” motion of the triosephosphate isomerase loop. Science 249:1425–1428
Williams JC, McDermott AE (1995) Dynamics of the flexible loop of triosephosphate isomerase: the loop motion is not ligand gated. Biochemistry 34:8309–8319
Berlow RB, Igumenova TI, Loria JP (2007) Value of a hydrogen bond in triosephosphate isomerase loop motion. Biochemistry 46:6001–6010
Sampson NS, Knowles JR (1992) Segmental motion in catalysis: investigation of a hydrogen bond critical for loop closure in the reaction of triosephosphate isomerase. Biochemistry 31:8488–8494
Derreumaux P, Schlick T (1998) The loop opening/closing motion of the enzyme triosephosphate isomerase. Biophys J 74:72–81
Wang Y, Berlow RB, Loria JP (2009) Role of loop-loop interactions in coordinating motions and enzymatic function in triosephosphate isomerase. Biochemistry 48:4548–4556
Casteleijn MG, Alahuhta M, Groebel K, El-Sayed I, Augustyns K, Lambeir AM, Neubauer P, Wierenga RK (2006) Functional role of the conserved active site proline of triosephosphate isomerase. Biochemistry 45:15483–15494
Yuksel KU, Sun AQ, Gracy RW, Schnackerz KD (1994) The hinged lid of yeast triose-phosphate isomerase. Determination of the energy barrier between the two conformations. J Biol Chem 269:5005–5008
Xu Y, Lorieau J, McDermott AE (2010) Triosephosphate isomerase: 15N and 13C chemical shift assignments and conformational change upon ligand binding by magic-angle spinning solid-state NMR spectroscopy. J Mol Biol 397:233–248
Benkovic SJ, Hammes GG, Hammes-Schiffer S (2008) Free-energy landscape of enzyme catalysis. Biochemistry 47:3317–3321
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We thank the Academy of Finland and the Finnish Cultural Foundation for their support. We thank Dr. Annemie Lambeir for critically reading the manuscript.
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Wierenga, R.K., Kapetaniou, E.G. & Venkatesan, R. Triosephosphate isomerase: a highly evolved biocatalyst. Cell. Mol. Life Sci. 67, 3961–3982 (2010). https://doi.org/10.1007/s00018-010-0473-9
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DOI: https://doi.org/10.1007/s00018-010-0473-9