Sequence Determinants of Quaternary Structure in Lumazine Synthase

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Riboflavin, an essential cofactor for all organisms, is biosynthesized in plants, fungi and microorganisms. The penultimate step in the pathway is catalyzed by the enzyme lumazine synthase. One of the most distinctive characteristics of this enzyme is that it is found in different species in two dif...

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Autores principales: Fornasari, M.S., Laplagne, D.A., Frankel, N., Cauerhff, A.A., Goldbaum, F.A., Echave, J.
Formato: Artículo publishedVersion
Publicado: 2004
Materias:
Evolutionary rates
Lumazine synthase
Quaternary structure
Structuralconstraints
lumazine
lumazine synthase
synthetase
unclassified drug
article
enzyme active site
enzyme structure
enzyme subunit
evolution
fungus
microorganism
nonhuman
nucleotide sequence
plant
protein assembly
protein quaternary structure
structure analysis
Base Sequence
Cluster Analysis
Databases, Genetic
Evolution, Molecular
Molecular Sequence Data
Multienzyme Complexes
Phylogeny
Protein Binding
Protein Structure, Quaternary
Sequence Alignment
Fungi
Miridae
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_07374038_v21_n1_p97_Fornasari
https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_07374038_v21_n1_p97_Fornasari_oai
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Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires
id I28-R145-paper_07374038_v21_n1_p97_Fornasari_oai
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spelling I28-R145-paper_07374038_v21_n1_p97_Fornasari_oai2024-08-16 Fornasari, M.S. Laplagne, D.A. Frankel, N. Cauerhff, A.A. Goldbaum, F.A. Echave, J. 2004 Riboflavin, an essential cofactor for all organisms, is biosynthesized in plants, fungi and microorganisms. The penultimate step in the pathway is catalyzed by the enzyme lumazine synthase. One of the most distinctive characteristics of this enzyme is that it is found in different species in two different quaternary structures, pentameric and icosahedral, built from practically the same structural monomeric unit. In fact, the icosahedral structure is best described as a capsid of twelve pentamers. Despite this noticeable difference, the active sites are virtually identical in all structurally studied members. Furthermore, the main regions involved in the catalysis are located at the interface between adjacent subunits in the pentamer. Thus, the two quaternary forms of the enzyme must meet similar structural requirements to achieve their function, but, at the same time, they should differ in the sequence traits responsible for the different quaternary structures observed. Here, we present a combined analysis that includes sequence-structure and evolutionary studies to find the sequence determinants of the different quaternary assemblies of this enzyme. A data set containing 86 sequences of the lumazine synthase family was recovered by sequence similarity searches. Seven of them had resolved three-dimensional structures. A subsequent phylogenetic reconstruction by maximum parsimony (MP) allowed division of the total set into two clusters in accord with their quaternary structure. The comparison between the patterns of three-dimensional contacts derived from the known three-dimensional structures and variation in sequence conservation revealed a significant shift in structural constraints of certain positions. Also, to explore the changes in functional constraints between the two groups, site-specific evolutionary rate shifts were analyzed. We found that the positions involved in icosahedral contacts suffer a larger increase in constraints than the rest. We found eight sequence sites that would be the most important icosahedral sequence determinants. We discuss our results and compare them with previous work. These findings should contribute to refinement of the current structural data, to the design of assays that explore the role of these positions, to the structural characterization of new sequences, and to initiation of a study of the underlying evolutionary mechanisms. Fil:Laplagne, D.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Frankel, N. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. application/pdf http://hdl.handle.net/20.500.12110/paper_07374038_v21_n1_p97_Fornasari info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar Mol. Biol. Evol. 2004;21(1):97-107 Evolutionary rates Lumazine synthase Quaternary structure Structuralconstraints lumazine lumazine synthase synthetase unclassified drug article enzyme active site enzyme structure enzyme subunit evolution fungus microorganism nonhuman nucleotide sequence plant protein assembly protein quaternary structure structure analysis Base Sequence Cluster Analysis Databases, Genetic Evolution, Molecular Molecular Sequence Data Multienzyme Complexes Phylogeny Protein Binding Protein Structure, Quaternary Sequence Alignment Fungi Miridae Sequence Determinants of Quaternary Structure in Lumazine Synthase info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_07374038_v21_n1_p97_Fornasari_oai
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-145
collection Repositorio Digital de la Universidad de Buenos Aires (UBA)
topic Evolutionary rates
Lumazine synthase
Quaternary structure
Structuralconstraints
lumazine
lumazine synthase
synthetase
unclassified drug
article
enzyme active site
enzyme structure
enzyme subunit
evolution
fungus
microorganism
nonhuman
nucleotide sequence
plant
protein assembly
protein quaternary structure
structure analysis
Base Sequence
Cluster Analysis
Databases, Genetic
Evolution, Molecular
Molecular Sequence Data
Multienzyme Complexes
Phylogeny
Protein Binding
Protein Structure, Quaternary
Sequence Alignment
Fungi
Miridae
spellingShingle Evolutionary rates
Lumazine synthase
Quaternary structure
Structuralconstraints
lumazine
lumazine synthase
synthetase
unclassified drug
article
enzyme active site
enzyme structure
enzyme subunit
evolution
fungus
microorganism
nonhuman
nucleotide sequence
plant
protein assembly
protein quaternary structure
structure analysis
Base Sequence
Cluster Analysis
Databases, Genetic
Evolution, Molecular
Molecular Sequence Data
Multienzyme Complexes
Phylogeny
Protein Binding
Protein Structure, Quaternary
Sequence Alignment
Fungi
Miridae
Fornasari, M.S.
Laplagne, D.A.
Frankel, N.
Cauerhff, A.A.
Goldbaum, F.A.
Echave, J.
Sequence Determinants of Quaternary Structure in Lumazine Synthase
topic_facet Evolutionary rates
Lumazine synthase
Quaternary structure
Structuralconstraints
lumazine
lumazine synthase
synthetase
unclassified drug
article
enzyme active site
enzyme structure
enzyme subunit
evolution
fungus
microorganism
nonhuman
nucleotide sequence
plant
protein assembly
protein quaternary structure
structure analysis
Base Sequence
Cluster Analysis
Databases, Genetic
Evolution, Molecular
Molecular Sequence Data
Multienzyme Complexes
Phylogeny
Protein Binding
Protein Structure, Quaternary
Sequence Alignment
Fungi
Miridae
description Riboflavin, an essential cofactor for all organisms, is biosynthesized in plants, fungi and microorganisms. The penultimate step in the pathway is catalyzed by the enzyme lumazine synthase. One of the most distinctive characteristics of this enzyme is that it is found in different species in two different quaternary structures, pentameric and icosahedral, built from practically the same structural monomeric unit. In fact, the icosahedral structure is best described as a capsid of twelve pentamers. Despite this noticeable difference, the active sites are virtually identical in all structurally studied members. Furthermore, the main regions involved in the catalysis are located at the interface between adjacent subunits in the pentamer. Thus, the two quaternary forms of the enzyme must meet similar structural requirements to achieve their function, but, at the same time, they should differ in the sequence traits responsible for the different quaternary structures observed. Here, we present a combined analysis that includes sequence-structure and evolutionary studies to find the sequence determinants of the different quaternary assemblies of this enzyme. A data set containing 86 sequences of the lumazine synthase family was recovered by sequence similarity searches. Seven of them had resolved three-dimensional structures. A subsequent phylogenetic reconstruction by maximum parsimony (MP) allowed division of the total set into two clusters in accord with their quaternary structure. The comparison between the patterns of three-dimensional contacts derived from the known three-dimensional structures and variation in sequence conservation revealed a significant shift in structural constraints of certain positions. Also, to explore the changes in functional constraints between the two groups, site-specific evolutionary rate shifts were analyzed. We found that the positions involved in icosahedral contacts suffer a larger increase in constraints than the rest. We found eight sequence sites that would be the most important icosahedral sequence determinants. We discuss our results and compare them with previous work. These findings should contribute to refinement of the current structural data, to the design of assays that explore the role of these positions, to the structural characterization of new sequences, and to initiation of a study of the underlying evolutionary mechanisms.
format Artículo
Artículo
publishedVersion
author Fornasari, M.S.
Laplagne, D.A.
Frankel, N.
Cauerhff, A.A.
Goldbaum, F.A.
Echave, J.
author_facet Fornasari, M.S.
Laplagne, D.A.
Frankel, N.
Cauerhff, A.A.
Goldbaum, F.A.
Echave, J.
author_sort Fornasari, M.S.
title Sequence Determinants of Quaternary Structure in Lumazine Synthase
title_short Sequence Determinants of Quaternary Structure in Lumazine Synthase
title_full Sequence Determinants of Quaternary Structure in Lumazine Synthase
title_fullStr Sequence Determinants of Quaternary Structure in Lumazine Synthase
title_full_unstemmed Sequence Determinants of Quaternary Structure in Lumazine Synthase
title_sort sequence determinants of quaternary structure in lumazine synthase
publishDate 2004
url http://hdl.handle.net/20.500.12110/paper_07374038_v21_n1_p97_Fornasari
https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_07374038_v21_n1_p97_Fornasari_oai
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