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==Human porphobilinogen deaminase in complex with DPM cofactor== | ==Human porphobilinogen deaminase in complex with DPM cofactor== | ||
<StructureSection load='5m7f' size='340' side='right' caption='[[5m7f]], [[Resolution|resolution]] 2.78Å' scene=''> | <StructureSection load='5m7f' size='340' side='right'caption='[[5m7f]], [[Resolution|resolution]] 2.78Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5m7f]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M7F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5M7F FirstGlance]. <br> | <table><tr><td colspan='2'>[[5m7f]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M7F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5M7F FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DPM:3-[5-{[3-(2-CARBOXYETHYL)-4-(CARBOXYMETHYL)-5-METHYL-1H-PYRROL-2-YL]METHYL}-4-(CARBOXYMETHYL)-1H-PYRROL-3-YL]PROPANOIC+ACID'>DPM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DPM:3-[5-{[3-(2-CARBOXYETHYL)-4-(CARBOXYMETHYL)-5-METHYL-1H-PYRROL-2-YL]METHYL}-4-(CARBOXYMETHYL)-1H-PYRROL-3-YL]PROPANOIC+ACID'>DPM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HMBS, PBGD, UPS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydroxymethylbilane_synthase Hydroxymethylbilane synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.61 2.5.1.61] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydroxymethylbilane_synthase Hydroxymethylbilane synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.61 2.5.1.61] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5m7f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m7f OCA], [http://pdbe.org/5m7f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5m7f RCSB], [http://www.ebi.ac.uk/pdbsum/5m7f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5m7f ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5m7f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m7f OCA], [http://pdbe.org/5m7f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5m7f RCSB], [http://www.ebi.ac.uk/pdbsum/5m7f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5m7f ProSAT]</span></td></tr> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/HEM3_HUMAN HEM3_HUMAN]] Tetrapolymerization of the monopyrrole PBG into the hydroxymethylbilane pre-uroporphyrinogen in several discrete steps. | [[http://www.uniprot.org/uniprot/HEM3_HUMAN HEM3_HUMAN]] Tetrapolymerization of the monopyrrole PBG into the hydroxymethylbilane pre-uroporphyrinogen in several discrete steps. | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human porphobilinogen deaminase (PBGD), the third enzyme in the heme pathway, catalyzes four times a single reaction to convert porphobilinogen into hydroxymethylbilane. Remarkably, PBGD employs a single active site during the process, with a distinct yet chemically equivalent bond formed each time. The four intermediate complexes of the enzyme have been biochemically validated and they can be isolated but they have never been structurally characterized other than the apo- and holo-enzyme bound to the cofactor. We present crystal structures for two human PBGD intermediates: PBGD loaded with the cofactor and with the reaction intermediate containing two additional substrate pyrrole rings. These results, combined with SAXS and NMR experiments, allow us to propose a mechanism for the reaction progression that requires less structural rearrangements than previously suggested: the enzyme slides a flexible loop over the growing-product active site cavity. The structures and the mechanism proposed for this essential reaction explain how a set of missense mutations result in acute intermittent porphyria. | |||
Structural basis of pyrrole polymerization in human porphobilinogen deaminase.,Pluta P, Roversi P, Bernardo-Seisdedos G, Rojas AL, Cooper JB, Gu S, Pickersgill RW, Millet O Biochim Biophys Acta Gen Subj. 2018 Sep;1862(9):1948-1955. doi:, 10.1016/j.bbagen.2018.06.013. Epub 2018 Jun 15. PMID:29908816<ref>PMID:29908816</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5m7f" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Porphobilinogen Deaminase|Porphobilinogen Deaminase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Hydroxymethylbilane synthase]] | [[Category: Hydroxymethylbilane synthase]] | ||
[[Category: Large Structures]] | |||
[[Category: Gu, S]] | [[Category: Gu, S]] | ||
[[Category: Millet, O]] | [[Category: Millet, O]] | ||