1i8j

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[[Image:1i8j.jpg|left|200px]]<br /><applet load="1i8j" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1i8j.jpg|left|200px]]
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caption="1i8j, resolution 1.9&Aring;" />
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'''CRYSTAL STRUCTURE OF PORPHOBILINOGEN SYNTHASE COMPLEXED WITH THE INHIBITOR 4,7-DIOXOSEBACIC ACID'''<br />
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{{Structure
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|PDB= 1i8j |SIZE=350|CAPTION= <scene name='initialview01'>1i8j</scene>, resolution 1.9&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=DSB:4,7-DIOXOSEBACIC ACID'>DSB</scene>
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|ACTIVITY= [http://en.wikipedia.org/wiki/Porphobilinogen_synthase Porphobilinogen synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.24 4.2.1.24]
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|GENE=
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}}
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'''CRYSTAL STRUCTURE OF PORPHOBILINOGEN SYNTHASE COMPLEXED WITH THE INHIBITOR 4,7-DIOXOSEBACIC ACID'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1I8J 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>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=DSB:'>DSB</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Porphobilinogen_synthase Porphobilinogen synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.24 4.2.1.24] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I8J OCA].
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1I8J is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I8J OCA].
==Reference==
==Reference==
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Mechanistic basis for suicide inactivation of porphobilinogen synthase by 4,7-dioxosebacic acid, an inhibitor that shows dramatic species selectivity., Kervinen J, Jaffe EK, Stauffer F, Neier R, Wlodawer A, Zdanov A, Biochemistry. 2001 Jul 27;40(28):8227-36. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11444968 11444968]
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Mechanistic basis for suicide inactivation of porphobilinogen synthase by 4,7-dioxosebacic acid, an inhibitor that shows dramatic species selectivity., Kervinen J, Jaffe EK, Stauffer F, Neier R, Wlodawer A, Zdanov A, Biochemistry. 2001 Jul 27;40(28):8227-36. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11444968 11444968]
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
[[Category: Porphobilinogen synthase]]
[[Category: Porphobilinogen synthase]]
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[[Category: zinc]]
[[Category: zinc]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:09:08 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:46:59 2008''

Revision as of 09:47, 20 March 2008

Image:1i8j.jpg


PDB ID 1i8j

Drag the structure with the mouse to rotate
, resolution 1.9Å
Ligands: , and
Activity: Porphobilinogen synthase, with EC number 4.2.1.24
Coordinates: save as pdb, mmCIF, xml



CRYSTAL STRUCTURE OF PORPHOBILINOGEN SYNTHASE COMPLEXED WITH THE INHIBITOR 4,7-DIOXOSEBACIC ACID


Overview

4,7-Dioxosebacic acid (4,7-DOSA) is an active site-directed irreversible inhibitor of porphobilinogen synthase (PBGS). PBGS catalyzes the first common step in the biosynthesis of the tetrapyrrole cofactors such as heme, vitamin B(12), and chlorophyll. 4,7-DOSA was designed as an analogue of a proposed reaction intermediate in the physiological PBGS-catalyzed condensation of two molecules of 5-aminolevulinic acid. As shown here, 4,7-DOSA exhibits time-dependent and dramatic species-specific inhibition of PBGS enzymes. IC(50) values vary from 1 microM to 2.4 mM for human, Escherichia coli, Bradyrhizobium japonicum, Pseudomonas aeruginosa, and pea enzymes. Those PBGS utilizing a catalytic Zn(2+) are more sensitive to 4,7-DOSA than those that do not. Weak inhibition of a human mutant PBGS establishes that the inactivation by 4,7-DOSA requires formation of a Schiff base to a lysine that normally forms a Schiff base intermediate to one substrate molecule. A 1.9 A resolution crystal structure of E. coli PBGS complexed with 4,7-DOSA (PDB code ) shows one dimer per asymmetric unit and reveals that the inhibitor forms two Schiff base linkages with each monomer, one to the normal Schiff base-forming Lys-246 and the other to a universally conserved "perturbing" Lys-194 (E. coli numbering). This is the first structure to show inhibitor binding at the second of two substrate-binding sites.

About this Structure

1I8J is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

Reference

Mechanistic basis for suicide inactivation of porphobilinogen synthase by 4,7-dioxosebacic acid, an inhibitor that shows dramatic species selectivity., Kervinen J, Jaffe EK, Stauffer F, Neier R, Wlodawer A, Zdanov A, Biochemistry. 2001 Jul 27;40(28):8227-36. PMID:11444968

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