1qr7
From Proteopedia
(New page: 200px<br /><applet load="1qr7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1qr7, resolution 2.6Å" /> '''CRYSTAL STRUCTURE OF ...) |
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| - | [[Image:1qr7.jpg|left|200px]]<br /><applet load="1qr7" size=" | + | [[Image:1qr7.jpg|left|200px]]<br /><applet load="1qr7" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1qr7, resolution 2.6Å" /> | caption="1qr7, resolution 2.6Å" /> | ||
'''CRYSTAL STRUCTURE OF PHENYLALANINE-REGULATED 3-DEOXY-D-ARABINO-HEPTULOSONATE-7-PHOSPHATE SYNTHASE FROM ESCHERICHIA COLI COMPLEXED WITH PB2+ AND PEP'''<br /> | '''CRYSTAL STRUCTURE OF PHENYLALANINE-REGULATED 3-DEOXY-D-ARABINO-HEPTULOSONATE-7-PHOSPHATE SYNTHASE FROM ESCHERICHIA COLI COMPLEXED WITH PB2+ AND PEP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: In microorganisms and plants the first step in the common | + | BACKGROUND: In microorganisms and plants the first step in the common pathway leading to the biosynthesis of aromatic compounds is the stereospecific condensation of phosphoenolpyruvate (PEP) and D-erythrose-4-phosphate (E4P) giving rise to 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP). This reaction is catalyzed by DAHP synthase (DAHPS), a metal-activated enzyme, which in microorganisms is the target for negative-feedback regulation by pathway intermediates or by end products. In Escherichia coli there are three DAHPS isoforms, each specifically inhibited by one of the three aromatic amino acids. RESULTS: The crystal structure of the phenylalanine-regulated form of DAHPS complexed with PEP and Pb2+ (DAHPS(Phe)-PEP-Pb) was determined by multiple wavelength anomalous dispersion phasing utilizing the anomalous scattering of Pb2+. The tetramer consists of two tight dimers. The monomers of the tight dimer are coupled by extensive interactions including a pair of three-stranded, intersubunit beta sheets. The monomer (350 residues) is a (beta/alpha)8 barrel with several additional beta strands and alpha helices. The PEP and Pb2+ are at the C-ends of the beta strands of the barrel, as is SO4(2-), inferred to occupy the position of the phosphate of E4P. Mutations that reduce feedback inhibition cluster about a cavity near the twofold axis of the tight dimer and are centered approximately 15 A from the active site, indicating the location of a separate regulatory site. CONCLUSIONS: The crystal structure of DAHPS(Phe)-PEP-Pb reveals the active site of this key enzyme of aromatic biosynthesis and indicates the probable site of inhibitor binding. This is the first reported structure of a DAHPS; the structure of its two paralogs and of a variety of orthologs should now be readily determined by molecular replacement. |
==About this Structure== | ==About this Structure== | ||
| - | 1QR7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with PB, SO4 and PEP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3-deoxy-7-phosphoheptulonate_synthase 3-deoxy-7-phosphoheptulonate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.54 2.5.1.54] Full crystallographic information is available from [http:// | + | 1QR7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=PB:'>PB</scene>, <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=PEP:'>PEP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3-deoxy-7-phosphoheptulonate_synthase 3-deoxy-7-phosphoheptulonate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.54 2.5.1.54] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QR7 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Bauerle, R | + | [[Category: Bauerle, R H.]] |
| - | [[Category: Kretsinger, R | + | [[Category: Kretsinger, R H.]] |
| - | [[Category: Shumilin, I | + | [[Category: Shumilin, I A.]] |
[[Category: PB]] | [[Category: PB]] | ||
[[Category: PEP]] | [[Category: PEP]] | ||
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[[Category: beta-alpha-barrel]] | [[Category: beta-alpha-barrel]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:42:51 2008'' |
Revision as of 12:42, 21 February 2008
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CRYSTAL STRUCTURE OF PHENYLALANINE-REGULATED 3-DEOXY-D-ARABINO-HEPTULOSONATE-7-PHOSPHATE SYNTHASE FROM ESCHERICHIA COLI COMPLEXED WITH PB2+ AND PEP
Overview
BACKGROUND: In microorganisms and plants the first step in the common pathway leading to the biosynthesis of aromatic compounds is the stereospecific condensation of phosphoenolpyruvate (PEP) and D-erythrose-4-phosphate (E4P) giving rise to 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP). This reaction is catalyzed by DAHP synthase (DAHPS), a metal-activated enzyme, which in microorganisms is the target for negative-feedback regulation by pathway intermediates or by end products. In Escherichia coli there are three DAHPS isoforms, each specifically inhibited by one of the three aromatic amino acids. RESULTS: The crystal structure of the phenylalanine-regulated form of DAHPS complexed with PEP and Pb2+ (DAHPS(Phe)-PEP-Pb) was determined by multiple wavelength anomalous dispersion phasing utilizing the anomalous scattering of Pb2+. The tetramer consists of two tight dimers. The monomers of the tight dimer are coupled by extensive interactions including a pair of three-stranded, intersubunit beta sheets. The monomer (350 residues) is a (beta/alpha)8 barrel with several additional beta strands and alpha helices. The PEP and Pb2+ are at the C-ends of the beta strands of the barrel, as is SO4(2-), inferred to occupy the position of the phosphate of E4P. Mutations that reduce feedback inhibition cluster about a cavity near the twofold axis of the tight dimer and are centered approximately 15 A from the active site, indicating the location of a separate regulatory site. CONCLUSIONS: The crystal structure of DAHPS(Phe)-PEP-Pb reveals the active site of this key enzyme of aromatic biosynthesis and indicates the probable site of inhibitor binding. This is the first reported structure of a DAHPS; the structure of its two paralogs and of a variety of orthologs should now be readily determined by molecular replacement.
About this Structure
1QR7 is a Single protein structure of sequence from Escherichia coli with , and as ligands. Active as 3-deoxy-7-phosphoheptulonate synthase, with EC number 2.5.1.54 Full crystallographic information is available from OCA.
Reference
Crystal structure of phenylalanine-regulated 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from Escherichia coli., Shumilin IA, Kretsinger RH, Bauerle RH, Structure. 1999 Jul 15;7(7):865-75. PMID:10425687
Page seeded by OCA on Thu Feb 21 14:42:51 2008
