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| | <StructureSection load='1l6y' size='340' side='right'caption='[[1l6y]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='1l6y' size='340' side='right'caption='[[1l6y]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1l6y]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L6Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L6Y FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1l6y]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L6Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L6Y FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4OX:4-OXODECANEDIOIC+ACID'>4OX</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4OX:4-OXODECANEDIOIC+ACID'>4OX</scene>, <scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1i8j|1i8j]], [[1l6s|1l6s]]</div></td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Porphobilinogen_synthase Porphobilinogen synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.24 4.2.1.24] </span></td></tr>
| + | |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1l6y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l6y OCA], [https://pdbe.org/1l6y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l6y RCSB], [https://www.ebi.ac.uk/pdbsum/1l6y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l6y ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1l6y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l6y OCA], [https://pdbe.org/1l6y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l6y RCSB], [https://www.ebi.ac.uk/pdbsum/1l6y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l6y ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/HEM2_ECOLI HEM2_ECOLI]] Catalyzes an early step in the biosynthesis of tetrapyrroles. Binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen.
| + | [https://www.uniprot.org/uniprot/HEM2_ECOLI HEM2_ECOLI] Catalyzes an early step in the biosynthesis of tetrapyrroles. Binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus coli migula 1895]] | + | [[Category: Escherichia coli]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Porphobilinogen synthase]]
| + | [[Category: Jaffe EK]] |
| - | [[Category: Jaffe, E K]] | + | [[Category: Kervinen J]] |
| - | [[Category: Kervinen, J]] | + | [[Category: Martins J]] |
| - | [[Category: Martins, J]] | + | [[Category: Neier R]] |
| - | [[Category: Neier, R]] | + | [[Category: Stauffer F]] |
| - | [[Category: Stauffer, F]] | + | [[Category: Wlodawer A]] |
| - | [[Category: Wlodawer, A]] | + | [[Category: Zdanov A]] |
| - | [[Category: Zdanov, A]] | + | |
| - | [[Category: Dehydratase]]
| + | |
| - | [[Category: Lyase]]
| + | |
| Structural highlights
1l6y is a 2 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.9Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
HEM2_ECOLI Catalyzes an early step in the biosynthesis of tetrapyrroles. Binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Porphobilinogen synthase (PBGS) catalyzes the condensation of two molecules of 5-aminolevulinic acid (ALA), an essential step in tetrapyrrole biosynthesis. 4-Oxosebacic acid (4-OSA) and 4,7-dioxosebacic acid (4,7-DOSA) are bisubstrate reaction intermediate analogs for PBGS. We show that 4-OSA is an active site-directed irreversible inhibitor for Escherichia coli PBGS, whereas human, pea, Pseudomonas aeruginosa, and Bradyrhizobium japonicum PBGS are insensitive to inhibition by 4-OSA. Some variants of human PBGS (engineered to resemble E. coli PBGS) have increased sensitivity to inactivation by 4-OSA, suggesting a structural basis for the specificity. The specificity of 4-OSA as a PBGS inhibitor is significantly narrower than that of 4,7-DOSA. Comparison of the crystal structures for E. coli PBGS inactivated by 4-OSA versus 4,7-DOSA shows significant variation in the half of the inhibitor that mimics the second substrate molecule (A-side ALA). Compensatory changes occur in the structure of the active site lid, which suggests that similar changes normally occur to accommodate numerous hybridization changes that must occur at C3 of A-side ALA during the PBGS-catalyzed reaction. A comparison of these with other PBGS structures identifies highly conserved active site water molecules, which are isolated from bulk solvent and implicated as proton acceptors in the PBGS-catalyzed reaction.
Species-specific inhibition of porphobilinogen synthase by 4-oxosebacic acid.,Jaffe EK, Kervinen J, Martins J, Stauffer F, Neier R, Wlodawer A, Zdanov A J Biol Chem. 2002 May 31;277(22):19792-9. Epub 2002 Mar 21. PMID:11909869[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jaffe EK, Kervinen J, Martins J, Stauffer F, Neier R, Wlodawer A, Zdanov A. Species-specific inhibition of porphobilinogen synthase by 4-oxosebacic acid. J Biol Chem. 2002 May 31;277(22):19792-9. Epub 2002 Mar 21. PMID:11909869 doi:10.1074/jbc.M201486200
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