Substrate channeling: Molecular bases
Mario Milani, Alessandra Pesce, Martino Bolognesi, Alessio Bocedi, Paolo Ascenzi
Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani
Substrate channeling (or tunneling) is the process of non-covalent direct transfer of a reaction intermediate from the active site of one enzyme to the catalytic center of a second enzyme without prior dissociation into the bulk solvent. Substrate channeling can occur within protein matrix tunnels or along electrostatic highways crossing the surface of multifunctional enzymes, of tightly associated multienzyme complexes, or of transient multienzyme complexes. Substrate channeling has been proposed (i) to decrease the transit time of reaction intermediates, (ii) to prevent the loss of reaction intermediates by diffusion, (iii) to protect labile reaction intermediates from solvent, (iv) to sequester reaction intermediates that are toxic to the cell, (v) to circumvent unfavorable equilibria, (vi) to forestall the entrance of reaction intermediates into competing metabolic pathways, (vii) to prevent the build-up of excess reaction intermediates, and (viii) to closely regulate a block of consecutive reactions within a metabolic pathway or in a multistep catalytic cycle. The three-dimensional structures of Escherichia coli carbamoyl-phosphate synthetase and Leishmania major dihydrofolate reductase-thymidylate synthase beautifully exemplify the concept of substrate channeling.
Biochemistry and Molecular Biology Education
https://doi.org/10.1002/bmb.2003.494031040239
Reaction intermediates
Metabolic Networks and Pathways
Multifunctional Enzymes
Carbamyl Phosphate
Ligases
Catalytic Domain
thymidylate synthase-dihydrofolate reductase
Electrostatic highways
Escherichia coli carbamoyl-phosphate synthetase
Leishmania major dihydrofolate reductase-thymidylate synthase
Protein matrix tunnels
Substrate channeling
Milani, M., Pesce, A., Bolognesi, M., Bocedi, A., & Ascenzi, P. (2003). Substrate channeling: Molecular bases. Biochemistry and Molecular Biology Education, 31(4), 228-233. https://doi.org/10.1002/bmb.2003.494031040239
Substrate channeling : Molecular bases. / Milani, Mario; Pesce, Alessandra; Bolognesi, Martino; Bocedi, Alessio; Ascenzi, Paolo.
In: Biochemistry and Molecular Biology Education, Vol. 31, No. 4, 07.2003, p. 228-233.
Milani, M, Pesce, A, Bolognesi, M, Bocedi, A & Ascenzi, P 2003, 'Substrate channeling: Molecular bases', Biochemistry and Molecular Biology Education, vol. 31, no. 4, pp. 228-233. https://doi.org/10.1002/bmb.2003.494031040239
Milani M, Pesce A, Bolognesi M, Bocedi A, Ascenzi P. Substrate channeling: Molecular bases. Biochemistry and Molecular Biology Education. 2003 Jul;31(4):228-233. https://doi.org/10.1002/bmb.2003.494031040239
Milani, Mario ; Pesce, Alessandra ; Bolognesi, Martino ; Bocedi, Alessio ; Ascenzi, Paolo. / Substrate channeling : Molecular bases. In: Biochemistry and Molecular Biology Education. 2003 ; Vol. 31, No. 4. pp. 228-233.
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title = "Substrate channeling: Molecular bases",
abstract = "Substrate channeling (or tunneling) is the process of non-covalent direct transfer of a reaction intermediate from the active site of one enzyme to the catalytic center of a second enzyme without prior dissociation into the bulk solvent. Substrate channeling can occur within protein matrix tunnels or along electrostatic highways crossing the surface of multifunctional enzymes, of tightly associated multienzyme complexes, or of transient multienzyme complexes. Substrate channeling has been proposed (i) to decrease the transit time of reaction intermediates, (ii) to prevent the loss of reaction intermediates by diffusion, (iii) to protect labile reaction intermediates from solvent, (iv) to sequester reaction intermediates that are toxic to the cell, (v) to circumvent unfavorable equilibria, (vi) to forestall the entrance of reaction intermediates into competing metabolic pathways, (vii) to prevent the build-up of excess reaction intermediates, and (viii) to closely regulate a block of consecutive reactions within a metabolic pathway or in a multistep catalytic cycle. The three-dimensional structures of Escherichia coli carbamoyl-phosphate synthetase and Leishmania major dihydrofolate reductase-thymidylate synthase beautifully exemplify the concept of substrate channeling.",
keywords = "Electrostatic highways, Escherichia coli carbamoyl-phosphate synthetase, Leishmania major dihydrofolate reductase-thymidylate synthase, Protein matrix tunnels, Substrate channeling",
author = "Mario Milani and Alessandra Pesce and Martino Bolognesi and Alessio Bocedi and Paolo Ascenzi",
doi = "10.1002/bmb.2003.494031040239",
journal = "Biochemistry and Molecular Biology Education",
T1 - Substrate channeling
T2 - Molecular bases
AU - Milani, Mario
AU - Pesce, Alessandra
AU - Bolognesi, Martino
AU - Bocedi, Alessio
AU - Ascenzi, Paolo
N2 - Substrate channeling (or tunneling) is the process of non-covalent direct transfer of a reaction intermediate from the active site of one enzyme to the catalytic center of a second enzyme without prior dissociation into the bulk solvent. Substrate channeling can occur within protein matrix tunnels or along electrostatic highways crossing the surface of multifunctional enzymes, of tightly associated multienzyme complexes, or of transient multienzyme complexes. Substrate channeling has been proposed (i) to decrease the transit time of reaction intermediates, (ii) to prevent the loss of reaction intermediates by diffusion, (iii) to protect labile reaction intermediates from solvent, (iv) to sequester reaction intermediates that are toxic to the cell, (v) to circumvent unfavorable equilibria, (vi) to forestall the entrance of reaction intermediates into competing metabolic pathways, (vii) to prevent the build-up of excess reaction intermediates, and (viii) to closely regulate a block of consecutive reactions within a metabolic pathway or in a multistep catalytic cycle. The three-dimensional structures of Escherichia coli carbamoyl-phosphate synthetase and Leishmania major dihydrofolate reductase-thymidylate synthase beautifully exemplify the concept of substrate channeling.
AB - Substrate channeling (or tunneling) is the process of non-covalent direct transfer of a reaction intermediate from the active site of one enzyme to the catalytic center of a second enzyme without prior dissociation into the bulk solvent. Substrate channeling can occur within protein matrix tunnels or along electrostatic highways crossing the surface of multifunctional enzymes, of tightly associated multienzyme complexes, or of transient multienzyme complexes. Substrate channeling has been proposed (i) to decrease the transit time of reaction intermediates, (ii) to prevent the loss of reaction intermediates by diffusion, (iii) to protect labile reaction intermediates from solvent, (iv) to sequester reaction intermediates that are toxic to the cell, (v) to circumvent unfavorable equilibria, (vi) to forestall the entrance of reaction intermediates into competing metabolic pathways, (vii) to prevent the build-up of excess reaction intermediates, and (viii) to closely regulate a block of consecutive reactions within a metabolic pathway or in a multistep catalytic cycle. The three-dimensional structures of Escherichia coli carbamoyl-phosphate synthetase and Leishmania major dihydrofolate reductase-thymidylate synthase beautifully exemplify the concept of substrate channeling.
KW - Electrostatic highways
KW - Escherichia coli carbamoyl-phosphate synthetase
KW - Leishmania major dihydrofolate reductase-thymidylate synthase
KW - Protein matrix tunnels
KW - Substrate channeling
U2 - 10.1002/bmb.2003.494031040239
DO - 10.1002/bmb.2003.494031040239
JO - Biochemistry and Molecular Biology Education
JF - Biochemistry and Molecular Biology Education
10.1002/bmb.2003.494031040239