Cooperative Fluctuations and Subunit Communication in Tryptophan Synthase
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- 作者：Ivet Bahar and Robert L. Jernigan
- 刊名：Biochemistry
- 出版年：1999
- 出版时间：March 23, 1999
- 年：1999
- 卷：38
- 期：12
- 页码：3478 - 3490
- 全文大小：306K
- 年卷期：v.38,no.12(March 23, 1999)
- ISSN：1520-4995
文摘
Tryptophan synthase (TRPS), with linearly arrayed subunits 
, catalyzes the last tworeactions in the biosynthesis of L-tryptophan. The two reactions take place in the respective - and-subunits of the enzyme, and the intermediate product, indole, is transferred from the - to the -sitethrough a 25 Å long hydrophobic tunnel. The occurrence of a unique ligand-mediated long-rangecooperativity for substrate channeling, and a quest to understand the mechanism of allosteric control andcoordination in metabolic cycles, have motivated many experimental studies on the structure and catalyticactivity of the TRPS 22 complex and its mutants. The dynamics of these complexes are analyzed hereusing a simple but rigorous theoretical approach, the Gaussian network model. Both wild-type and mutantstructures, in the unliganded and various liganded forms, are considered. The substrate binding site in the-subunit is found to be closely coupled to a group of hinge residues (77-89 and 376-379) nearthe - interface. These residues simultaneously control the anticorrelated motion of the two -subunits,and the opening or closing of the hydrophobic tunnel. The latter process is achieved by the large amplitudefluctuations of the so-called COMM domain in the same subunit. Intersubunit communications arestrengthened in the presence of external aldimines bound to the -site. The motions of the COMM coreresidues are coordinated with those of the - hinge residues 174-179 on the interfacial helix H6at the entrance of the hydrophobic tunnel. And the motions of H6 are coupled, via helix H1 and L6,to those of the loop L2 that includes the -subunit catalytically active residue Asp60. Overall, our analysissheds light on the molecular machinery underlying subunit communication, and identifies the residuesplaying a key role in the cooperative transmission of conformational motions across the two reactionsites.
, catalyzes the last tworeactions in the biosynthesis of L-tryptophan. The two reactions take place in the respective - and-subunits of the enzyme, and the intermediate product, indole, is transferred from the - to the -sitethrough a 25 Å long hydrophobic tunnel. The occurrence of a unique ligand-mediated long-rangecooperativity for substrate channeling, and a quest to understand the mechanism of allosteric control andcoordination in metabolic cycles, have motivated many experimental studies on the structure and catalyticactivity of the TRPS 22 complex and its mutants. The dynamics of these complexes are analyzed hereusing a simple but rigorous theoretical approach, the Gaussian network model. Both wild-type and mutantstructures, in the unliganded and various liganded forms, are considered. The substrate binding site in the-subunit is found to be closely coupled to a group of hinge residues (77-89 and 376-379) nearthe - interface. These residues simultaneously control the anticorrelated motion of the two -subunits,and the opening or closing of the hydrophobic tunnel. The latter process is achieved by the large amplitudefluctuations of the so-called COMM domain in the same subunit. Intersubunit communications arestrengthened in the presence of external aldimines bound to the -site. The motions of the COMM coreresidues are coordinated with those of the - hinge residues 174-179 on the interfacial helix H6at the entrance of the hydrophobic tunnel. And the motions of H6 are coupled, via helix H1 and L6,to those of the loop L2 that includes the -subunit catalytically active residue Asp60. Overall, our analysissheds light on the molecular machinery underlying subunit communication, and identifies the residuesplaying a key role in the cooperative transmission of conformational motions across the two reactionsites.