1ps6
From Proteopedia
(New page: 200px<br /><applet load="1ps6" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ps6, resolution 2.25Å" /> '''Crystal structure of...) |
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| - | [[Image:1ps6.jpg|left|200px]]<br /><applet load="1ps6" size=" | + | [[Image:1ps6.jpg|left|200px]]<br /><applet load="1ps6" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ps6, resolution 2.25Å" /> | caption="1ps6, resolution 2.25Å" /> | ||
'''Crystal structure of E.coli PdxA'''<br /> | '''Crystal structure of E.coli PdxA'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Pyridoxal 5'-phosphate is an essential cofactor for many enzymes | + | Pyridoxal 5'-phosphate is an essential cofactor for many enzymes responsible for the metabolic conversions of amino acids. Two pathways for its de novo synthesis are known. The pathway utilized by Escherichia coli consists of six enzymatic steps catalyzed by six different enzymes. The fourth step is catalyzed by 4-hydroxythreonine-4-phosphate dehydrogenase (PdxA, E.C. 1.1.1.262), which converts 4-hydroxy-l-threonine phosphate (HTP) to 3-amino-2-oxopropyl phosphate. This divalent metal ion-dependent enzyme has a strict requirement for the phosphate ester form of the substrate HTP, but can utilize either NADP+ or NAD+ as redox cofactor. We report the crystal structure of E. coli PdxA and its complex with HTP and Zn2+. The protein forms tightly bound dimers. Each monomer has an alpha/beta/alpha-fold and can be divided into two subdomains. The active site is located at the dimer interface, within a cleft between the two subdomains and involves residues from both monomers. A Zn2+ ion is bound within each active site, coordinated by three conserved histidine residues from both monomers. In addition two conserved amino acids, Asp247 and Asp267, play a role in maintaining integrity of the active site. The substrate is anchored to the enzyme by the interactions of its phospho group and by coordination of the amino and hydroxyl groups by the Zn2+ ion. PdxA is structurally similar to, but limited in sequence similarity with isocitrate dehydrogenase and isopropylmalate dehydrogenase. These structural similarities and the comparison with a NADP-bound isocitrate dehydrogenase suggest that the cofactor binding mode of PdxA is very similar to that of the other two enzymes and that PdxA catalyzes a stepwise oxidative decarboxylation of the substrate HTP. |
==About this Structure== | ==About this Structure== | ||
| - | 1PS6 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 ZN and 4TP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/4-hydroxythreonine-4-phosphate_dehydrogenase 4-hydroxythreonine-4-phosphate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.262 1.1.1.262] Full crystallographic information is available from [http:// | + | 1PS6 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=ZN:'>ZN</scene> and <scene name='pdbligand=4TP:'>4TP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/4-hydroxythreonine-4-phosphate_dehydrogenase 4-hydroxythreonine-4-phosphate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.262 1.1.1.262] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PS6 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Banks, J.]] | [[Category: Banks, J.]] | ||
| - | [[Category: Cane, D | + | [[Category: Cane, D E.]] |
[[Category: Cygler, M.]] | [[Category: Cygler, M.]] | ||
[[Category: Li, Y.]] | [[Category: Li, Y.]] | ||
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[[Category: pdxa; 4-hydroxythreonine-4-phosphate dehydrogenase; pyridoxal 5'-phosphate biosynthesis; plp]] | [[Category: pdxa; 4-hydroxythreonine-4-phosphate dehydrogenase; pyridoxal 5'-phosphate biosynthesis; plp]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:32:02 2008'' |
Revision as of 12:32, 21 February 2008
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Crystal structure of E.coli PdxA
Overview
Pyridoxal 5'-phosphate is an essential cofactor for many enzymes responsible for the metabolic conversions of amino acids. Two pathways for its de novo synthesis are known. The pathway utilized by Escherichia coli consists of six enzymatic steps catalyzed by six different enzymes. The fourth step is catalyzed by 4-hydroxythreonine-4-phosphate dehydrogenase (PdxA, E.C. 1.1.1.262), which converts 4-hydroxy-l-threonine phosphate (HTP) to 3-amino-2-oxopropyl phosphate. This divalent metal ion-dependent enzyme has a strict requirement for the phosphate ester form of the substrate HTP, but can utilize either NADP+ or NAD+ as redox cofactor. We report the crystal structure of E. coli PdxA and its complex with HTP and Zn2+. The protein forms tightly bound dimers. Each monomer has an alpha/beta/alpha-fold and can be divided into two subdomains. The active site is located at the dimer interface, within a cleft between the two subdomains and involves residues from both monomers. A Zn2+ ion is bound within each active site, coordinated by three conserved histidine residues from both monomers. In addition two conserved amino acids, Asp247 and Asp267, play a role in maintaining integrity of the active site. The substrate is anchored to the enzyme by the interactions of its phospho group and by coordination of the amino and hydroxyl groups by the Zn2+ ion. PdxA is structurally similar to, but limited in sequence similarity with isocitrate dehydrogenase and isopropylmalate dehydrogenase. These structural similarities and the comparison with a NADP-bound isocitrate dehydrogenase suggest that the cofactor binding mode of PdxA is very similar to that of the other two enzymes and that PdxA catalyzes a stepwise oxidative decarboxylation of the substrate HTP.
About this Structure
1PS6 is a Single protein structure of sequence from Escherichia coli with and as ligands. Active as 4-hydroxythreonine-4-phosphate dehydrogenase, with EC number 1.1.1.262 Full crystallographic information is available from OCA.
Reference
Crystal structure of Escherichia coli PdxA, an enzyme involved in the pyridoxal phosphate biosynthesis pathway., Sivaraman J, Li Y, Banks J, Cane DE, Matte A, Cygler M, J Biol Chem. 2003 Oct 31;278(44):43682-90. Epub 2003 Aug 1. PMID:12896974
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