1pjs
From Proteopedia
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| - | [[Image:1pjs.gif|left|200px]] | ||
| - | + | ==The co-crystal structure of CysG, the multifunctional methyltransferase/dehydrogenase/ferrochelatase for siroheme synthesis, in complex with it NAD cofactor== | |
| - | + | <StructureSection load='1pjs' size='340' side='right'caption='[[1pjs]], [[Resolution|resolution]] 2.40Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | | | + | <table><tr><td colspan='2'>[[1pjs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Salmonella_enterica_subsp._enterica_serovar_Typhimurium Salmonella enterica subsp. enterica serovar Typhimurium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PJS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PJS FirstGlance]. <br> |
| - | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> | |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></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=1pjs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pjs OCA], [https://pdbe.org/1pjs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pjs RCSB], [https://www.ebi.ac.uk/pdbsum/1pjs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pjs ProSAT]</span></td></tr> | |
| - | + | </table> | |
| - | + | == Function == | |
| - | + | [https://www.uniprot.org/uniprot/CYSG_SALTY CYSG_SALTY] Multifunctional enzyme that catalyzes the SAM-dependent methylations of uroporphyrinogen III at position C-2 and C-7 to form precorrin-2 via precorrin-1. Then it catalyzes the NAD-dependent ring dehydrogenation of precorrin-2 to yield sirohydrochlorin. Finally, it catalyzes the ferrochelation of sirohydrochlorin to yield siroheme.<ref>PMID:14595395</ref> | |
| - | + | == Evolutionary Conservation == | |
| - | + | [[Image:Consurf_key_small.gif|200px|right]] | |
| - | + | Check<jmol> | |
| - | + | <jmolCheckbox> | |
| - | == | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pj/1pjs_consurf.spt"</scriptWhenChecked> |
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1pjs ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
Sulfur metabolism depends on the iron-containing porphinoid siroheme. In Salmonella enterica, the S-adenosyl-L-methionine (SAM)-dependent bismethyltransferase, dehydrogenase and ferrochelatase, CysG, synthesizes siroheme from uroporphyrinogen III (uro'gen III). The reactions mediated by CysG encompass two branchpoint intermediates in tetrapyrrole biosynthesis, diverting flux first from protoporphyrin IX biosynthesis and then from cobalamin (vitamin B(12)) biosynthesis. We determined the first structure of this multifunctional siroheme synthase by X-ray crystallography. CysG is a homodimeric gene fusion product containing two structurally independent modules: a bismethyltransferase and a dual-function dehydrogenase-chelatase. The methyltransferase active site is a deep groove with a hydrophobic patch surrounded by hydrogen bond donors. This asymmetric arrangement of amino acids may be important in directing substrate binding. Notably, our structure shows that CysG is a phosphoprotein. From mutational analysis of the post-translationally modified serine, we suggest a conserved role for phosphorylation in inhibiting dehydrogenase activity and modulating metabolic flux between siroheme and cobalamin pathways. | Sulfur metabolism depends on the iron-containing porphinoid siroheme. In Salmonella enterica, the S-adenosyl-L-methionine (SAM)-dependent bismethyltransferase, dehydrogenase and ferrochelatase, CysG, synthesizes siroheme from uroporphyrinogen III (uro'gen III). The reactions mediated by CysG encompass two branchpoint intermediates in tetrapyrrole biosynthesis, diverting flux first from protoporphyrin IX biosynthesis and then from cobalamin (vitamin B(12)) biosynthesis. We determined the first structure of this multifunctional siroheme synthase by X-ray crystallography. CysG is a homodimeric gene fusion product containing two structurally independent modules: a bismethyltransferase and a dual-function dehydrogenase-chelatase. The methyltransferase active site is a deep groove with a hydrophobic patch surrounded by hydrogen bond donors. This asymmetric arrangement of amino acids may be important in directing substrate binding. Notably, our structure shows that CysG is a phosphoprotein. From mutational analysis of the post-translationally modified serine, we suggest a conserved role for phosphorylation in inhibiting dehydrogenase activity and modulating metabolic flux between siroheme and cobalamin pathways. | ||
| - | + | CysG structure reveals tetrapyrrole-binding features and novel regulation of siroheme biosynthesis.,Stroupe ME, Leech HK, Daniels DS, Warren MJ, Getzoff ED Nat Struct Biol. 2003 Dec;10(12):1064-73. Epub 2003 Nov 2. PMID:14595395<ref>PMID:14595395</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 1pjs" style="background-color:#fffaf0;"></div> | |
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| - | + | ==See Also== | |
| + | *[[Siroheme synthase|Siroheme synthase]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Salmonella enterica subsp. enterica serovar Typhimurium]] | ||
| + | [[Category: Daniels DS]] | ||
| + | [[Category: Getzoff ED]] | ||
| + | [[Category: Leech HK]] | ||
| + | [[Category: Stroupe ME]] | ||
| + | [[Category: Warren MJ]] | ||
Current revision
The co-crystal structure of CysG, the multifunctional methyltransferase/dehydrogenase/ferrochelatase for siroheme synthesis, in complex with it NAD cofactor
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