1i8d
From Proteopedia
(New page: 200px<br /><applet load="1i8d" size="450" color="white" frame="true" align="right" spinBox="true" caption="1i8d, resolution 2.0Å" /> '''CRYSTAL STRUCTURE OF ...) |
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| - | [[Image:1i8d.gif|left|200px]]<br /><applet load="1i8d" size=" | + | [[Image:1i8d.gif|left|200px]]<br /><applet load="1i8d" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1i8d, resolution 2.0Å" /> | caption="1i8d, resolution 2.0Å" /> | ||
'''CRYSTAL STRUCTURE OF RIBOFLAVIN SYNTHASE'''<br /> | '''CRYSTAL STRUCTURE OF RIBOFLAVIN SYNTHASE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: Riboflavin synthase catalyzes the dismutation of two molecules | + | BACKGROUND: Riboflavin synthase catalyzes the dismutation of two molecules of 6,7-dimethyl-8-(1'-D-ribityl)-lumazine to yield riboflavin and 4-ribitylamino-5-amino-2,6-dihydroxypyrimidine. The homotrimer of 23 kDa subunits has no cofactor requirements for catalysis. The enzyme is nonexistent in humans and is an attractive target for antimicrobial agents of organisms whose pathogenicity depends on their ability to biosynthesize riboflavin. RESULTS: The first three-dimensional structure of the enzyme was determined at 2.0 A resolution using the multiwavelength anomalous diffraction (MAD) method on the Escherichia coli protein containing selenomethionine residues. The homotrimer consists of an asymmetric assembly of monomers, each of which comprises two similar beta barrels and a C-terminal alpha helix. The similar beta barrels within the monomer confirm a prediction of pseudo two-fold symmetry that is inferred from the sequence similarity between the two halves of the protein. The beta barrels closely resemble folds found in phthalate dioxygenase reductase and other flavoproteins. CONCLUSIONS: The three active sites of the trimer are proposed to lie between pairs of monomers in which residues conserved among species reside, including two Asp-His-Ser triads and dyads of Cys-Ser and His-Thr. The proposed active sites are located where FMN (an analog of riboflavin) is modeled from an overlay of the beta barrels of phthalate dioxygenase reductase and riboflavin synthase. In the trimer, one active site is formed, and the other two active sites are wide open and exposed to solvent. The nature of the trimer configuration suggests that only one active site can be formed and be catalytically competent at a time. |
==About this Structure== | ==About this Structure== | ||
| - | 1I8D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Active as [http://en.wikipedia.org/wiki/Riboflavin_synthase Riboflavin synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.9 2.5.1.9] Full crystallographic information is available from [http:// | + | 1I8D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Active as [http://en.wikipedia.org/wiki/Riboflavin_synthase Riboflavin synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.9 2.5.1.9] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I8D OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Riboflavin synthase]] | [[Category: Riboflavin synthase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Calabrese, J | + | [[Category: Calabrese, J C.]] |
| - | [[Category: Jordan, D | + | [[Category: Jordan, D B.]] |
| - | [[Category: Liao, D | + | [[Category: Liao, D I.]] |
| - | [[Category: Viitanen, P | + | [[Category: Viitanen, P V.]] |
[[Category: Wawrzak, Z.]] | [[Category: Wawrzak, Z.]] | ||
[[Category: antimicrobial target]] | [[Category: antimicrobial target]] | ||
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[[Category: structure-based design]] | [[Category: structure-based design]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:09:06 2008'' |
Revision as of 11:09, 21 February 2008
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CRYSTAL STRUCTURE OF RIBOFLAVIN SYNTHASE
Overview
BACKGROUND: Riboflavin synthase catalyzes the dismutation of two molecules of 6,7-dimethyl-8-(1'-D-ribityl)-lumazine to yield riboflavin and 4-ribitylamino-5-amino-2,6-dihydroxypyrimidine. The homotrimer of 23 kDa subunits has no cofactor requirements for catalysis. The enzyme is nonexistent in humans and is an attractive target for antimicrobial agents of organisms whose pathogenicity depends on their ability to biosynthesize riboflavin. RESULTS: The first three-dimensional structure of the enzyme was determined at 2.0 A resolution using the multiwavelength anomalous diffraction (MAD) method on the Escherichia coli protein containing selenomethionine residues. The homotrimer consists of an asymmetric assembly of monomers, each of which comprises two similar beta barrels and a C-terminal alpha helix. The similar beta barrels within the monomer confirm a prediction of pseudo two-fold symmetry that is inferred from the sequence similarity between the two halves of the protein. The beta barrels closely resemble folds found in phthalate dioxygenase reductase and other flavoproteins. CONCLUSIONS: The three active sites of the trimer are proposed to lie between pairs of monomers in which residues conserved among species reside, including two Asp-His-Ser triads and dyads of Cys-Ser and His-Thr. The proposed active sites are located where FMN (an analog of riboflavin) is modeled from an overlay of the beta barrels of phthalate dioxygenase reductase and riboflavin synthase. In the trimer, one active site is formed, and the other two active sites are wide open and exposed to solvent. The nature of the trimer configuration suggests that only one active site can be formed and be catalytically competent at a time.
About this Structure
1I8D is a Single protein structure of sequence from Escherichia coli. Active as Riboflavin synthase, with EC number 2.5.1.9 Full crystallographic information is available from OCA.
Reference
Crystal structure of riboflavin synthase., Liao DI, Wawrzak Z, Calabrese JC, Viitanen PV, Jordan DB, Structure. 2001 May 9;9(5):399-408. PMID:11377200
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