1i8j
From Proteopedia
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|PDB= 1i8j |SIZE=350|CAPTION= <scene name='initialview01'>1i8j</scene>, resolution 1.9Å | |PDB= 1i8j |SIZE=350|CAPTION= <scene name='initialview01'>1i8j</scene>, resolution 1.9Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=DSB:4,7-DIOXOSEBACIC+ACID'>DSB</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
| - | |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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1i8j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i8j OCA], [http://www.ebi.ac.uk/pdbsum/1i8j PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1i8j RCSB]</span> | ||
}} | }} | ||
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[[Category: Wlodawer, A.]] | [[Category: Wlodawer, A.]] | ||
[[Category: Zdanov, A.]] | [[Category: Zdanov, A.]] | ||
| - | + | [[Category: 4,7-dioxosebacic acid]] | |
| - | + | ||
| - | + | ||
| - | [[Category: 4 | + | |
| - | + | ||
[[Category: heme biosynthesis]] | [[Category: heme biosynthesis]] | ||
[[Category: lyase]] | [[Category: lyase]] | ||
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[[Category: zinc]] | [[Category: zinc]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:16:10 2008'' |
Revision as of 18:16, 30 March 2008
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| , resolution 1.9Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Activity: | Porphobilinogen synthase, with EC number 4.2.1.24 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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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