Triose-phosphate Isomerase (TIM) of the Psychrophilic BacteriumVibrio marinus

Alvarez, Marco; Zeelen, J.P.; Mainfroid, Véronique; Rentier-Delrue, Françoise; Martial, Joseph; Wyns, Lode; Wierenga, Rik K.; Maes, Dominique

doi:10.1074/jbc.273.4.2199

Cited by 148 publications

(116 citation statements)

References 38 publications

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“…The only non-Gly residue that shows a positive 9 is Lys12 (49.5/52.5 and 54.7/50.9 in the A/B subunits of the 3PG and G3P complexes, respectively). Indeed, this residue has a positive 9 in the unbound PfTIM and also in enzymes from other sources (Noble et al, 1991;Alvarez et al, 1998;Zhang et al, 1994). The ligands were well de®ned in both the crystallographically independent subunits, although the ligands are better de®ned in one of the subunits than in the other.…”

Section: Figurementioning

confidence: 99%

Structures ofPlasmodium falciparumtriosephosphate isomerase complexed to substrate analogues: observation of the catalytic loop in the open conformation in the ligand-bound state

Parthasarathy

Balaram

et al. 2002

Acta Crystallogr D Biol Crystallogr

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The glycolytic enzymes of Plasmodium falciparum (Pf) are attractive drug targets as the parasites lack a functional tricarboxylic cycle and hence depend heavily on glycolysis for their energy requirements. Structural comparisons between Pf triosephosphate isomerase (PfTIM) and its human homologue have highlighted the important differences between the host and parasite enzymes [Velanker et al. (1997), Structure, 5, 751–761]. Structures of various PfTIM–ligand complexes have been determined in order to gain further insight into the mode of inhibitor binding to the parasite enzyme. Structures of two PfTIM–substrate analogue complexes, those of 3‐phosphoglycerate (3PG) and glycerol‐3‐phosphate (G3P), have been determined and refined at 2.4 Å resolution. Both complexes crystallized in the monoclinic space group P21, with a molecular dimer in the asymmetric unit. The novel aspect of these structures is the adoption of the `loop‐open' conformation, with the catalytic loop (loop 6, residues 166–176) positioned away from the active site; this loop is known to move by about 7 Å towards the active site upon inhibitor binding in other TIMs. The loop‐open form in the PfTIM complexes appears to be a consequence of the S96F mutation, which is specific to the enzymes from malarial parasites. Structural comparison with the corresponding complexes of Trypanosoma brucei TIM (TrypTIM) shows that extensive steric clashes may be anticipated between Phe96 and Ile172 in the `closed' conformation of the catalytic loop, preventing loop closure in PfTIM. Ser73 in PfTIM (Ala in all other known TIMs) appears to provide an anchoring water‐mediated hydrogen bond to the ligand, compensating for the loss of a stabilizing hydrogen bond from Gly171 NH in the closed‐loop liganded TIM structures.

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Section: Figurementioning

confidence: 99%

Structures ofPlasmodium falciparumtriosephosphate isomerase complexed to substrate analogues: observation of the catalytic loop in the open conformation in the ligand-bound state

Parthasarathy

Balaram

et al. 2002

Acta Crystallogr D Biol Crystallogr

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“…In addition to mutational studies, the involvement of these factors in protein adaptation is suggested from comparative studies between psychrophilic enzymes and their heat-stable homologues based on homology models and 3D structures. An increased number of crystallographic structures of psychrophilic enzymes from bacteria and cold-adapted fishes have been previously elucidated (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41) (29) and fish trypsin (37). Other structures should become available soon, as crystals of three other cold-active enzymes have been obtained (43)(44)(45).…”

Section: Psychrophilic Enzymesmentioning

confidence: 99%

Extreme catalysts from low-temperature environments

Hoyoux

Blaise

Collins

et al. 2004

Journal of Bioscience and Bioengineering

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Cold-loving or psychrophilic organisms are widely distributed in nature as a large part of the earth's surface is at temperatures around 0°C. To maintain metabolic rates and to prosper in cold environments, these extremophilic organisms have developed a vast array of adaptations. One main adaptive strategy developed in order to cope with the reduction of chemical reaction rates induced by low temperatures is the synthesis of cold-adapted or psychrophilic enzymes. These enzymes are characterized by a high catalytic activity at low temperatures associated with a low thermal stability. A study of protein adaptation strategies suggests that the high activity of psychrophilic enzymes could be achieved by the destabilization of the active site, allowing the catalytic center to be more flexible at low temperatures, whereas other protein regions may be destabilized or as rigid as their mesophilic counterparts. Due to these particular properties, psychrophilic enzymes offer a high potential not only for fundamental research but also for biotechnological applications.[Key words: psychrophile, extremophiles, cold adaptation, enzyme kinetics, flexibility strategy]Life under low-temperature conditions was identified as early as 1840 by Hooker, who observed that algae were associated with sea ice. In 1887, Forster was the first who reported that microorganisms isolated from fish could grow well at 0°C (1). The term "psychrophilic" was first used in 1902 by Schmidt-Nielsen to describe such cold-adapted organisms (2). Psychrophile is defined as an organism, prokaryotic or eukaryotic, living permanently at temperatures close to the freezing point of water in thermal equilibrium with the medium. Thus psychrophiles are numerous, including a large range of species of gram-positive and gram-negative bacteria, yeast, algae, marine invertebrates, insects and polar fish, and are widely distributed (3). Psychrophiles have developed mechanisms of adaptation to temperature including a huge range of structural and physiological adjustments in order to cope with the deleterious effect of low temperatures. Indeed, they display metabolic fluxes at low temperatures that are more or less comparable to those exhibited by closely related mesophiles living at moderate temperatures (4-6). This is explained by the capability of these psychrophilic organisms to produce "cold-adapted" enzymes which are able to cope with the reduction of chemical reaction rates induced by low temperatures. However, most cellular adaptations to low temperatures and the underlying molecular mechanisms are not fully understood and are still being investigated. Moreover, a study of proteins and enzymes from cold-adapted organisms is not only useful in the understanding of some general processes related to the protein structure and function but also in protein folding investigations. In addition, cold-active and heat-labile psychrophilic enzymes possess an interesting biotechnological potential.

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“…Although some features of the cold-adapted enzymes have been proposed on the basis of comparisons between the primary structures of the corresponding enzymes from various organisms with different ranges of growth temperature, it is difficult to distinguish exactly whether they are attributable to cold adaptation or to phylogenetic differences between the organisms (Sheridan et al, 2000). On the other hand, analyses of the crystal structures of cold-adapted enzymes has revealed the diversity of their mechanisms for cold adaptation (Fields & Somero, 1998;Russell et al, 1998;Kim et al, 1999;Alvarez et al, 1998;Bentahir et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Amino acid residues involved in cold adaptation of isocitrate lyase from a psychrophilic bacterium, Colwellia maris

Watanabe

2004

Microbiology

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To investigate the mechanism of cold adaptation of isocitrate lyase (ICL; EC 4.1.3.1) from the psychrophilic bacterium Colwellia maris, Gln207 and Gln217 of this enzyme were substituted by His and Lys, respectively, by site-directed mutagenesis. His184 and Lys194 of ICL from Escherichia coli, corresponding to the two Gln residues of C. maris ICL, are highly conserved in the ICLs of many organisms and are known to be essential for catalytic function. The mutated ICLs (Cm-Q207H and Cm-Q217K, respectively) and wild-type enzymes of C. maris and E. coli (Cm-WT and Ec-WT) with His-tagged peptides were overexpressed in E. coli cells and purified to homogeneity. Thermolabile Cm-WT and mutated ICLs were susceptible to digestion with trypsin, while relatively thermostable Ec-WT was resistant to trypsin digestion, suggesting that the thermostability and resistance to tryptic digestion of the ICLs are related. Cm-Q207H and Cm-Q217K showed specific activities similar to Cm-WT at temperatures between 30 6C and 40 6C, but their activities between 10 6C and 25 6C were decreased, indicating that the two Gln residues of the C. maris ICL play important roles in its cold adaptation. Phylogenetic analysis of ICLs from various organisms revealed that the C. maris ICL can be categorized in a novel group, subfamily 3, together with several eubacterial ICLs.

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Triose-phosphate Isomerase (TIM) of the Psychrophilic BacteriumVibrio marinus

Cited by 148 publications

References 38 publications

Structures ofPlasmodium falciparumtriosephosphate isomerase complexed to substrate analogues: observation of the catalytic loop in the open conformation in the ligand-bound state

Structures ofPlasmodium falciparumtriosephosphate isomerase complexed to substrate analogues: observation of the catalytic loop in the open conformation in the ligand-bound state

Extreme catalysts from low-temperature environments

Amino acid residues involved in cold adaptation of isocitrate lyase from a psychrophilic bacterium, Colwellia maris

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