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1pv8

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Revision as of 08:21, 24 February 2018

Crystal structure of a low activity F12L mutant of human porphobilinogen synthase

Structural highlights

1pv8 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	ALAD (HUMAN)
Activity:	Porphobilinogen synthase, with EC number 4.2.1.24
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[HEM2_HUMAN] Defects in ALAD are the cause of acute hepatic porphyria (AHEPP) [MIM:612740]. A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. AHP is characterized by attacks of gastrointestinal disturbances, abdominal colic, paralysis, and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors.^[1] ^[2] ^[3] ^[4] ^[5]

Function

[HEM2_HUMAN] 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.^[6] ^[7]

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 first common step in the biosynthesis of tetrapyrroles (such as heme and chlorophyll). Although the predominant oligomeric form of this enzyme, as inferred from many crystal structures, is that of a homo-octamer, a rare human PBGS allele, F12L, reveals the presence of a hexameric form. Rearrangement of an N-terminal arm is responsible for this oligomeric switch, which results in profound changes in kinetic behavior. The structural transition between octamer and hexamer must proceed through an unparalleled equilibrium containing two different dimer structures. The allosteric magnesium, present in most PBGS, has a binding site in the octamer but not in the hexamer. The unprecedented structural rearrangement reported here relates to the allosteric regulation of PBGS and suggests that alternative PBGS oligomers may function in a magnesium-dependent regulation of tetrapyrrole biosynthesis in plants and some bacteria.

Control of tetrapyrrole biosynthesis by alternate quaternary forms of porphobilinogen synthase.,Breinig S, Kervinen J, Stith L, Wasson AS, Fairman R, Wlodawer A, Zdanov A, Jaffe EK Nat Struct Biol. 2003 Sep;10(9):757-63. Epub 2003 Aug 3. PMID:12897770^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ishida N, Fujita H, Fukuda Y, Noguchi T, Doss M, Kappas A, Sassa S. Cloning and expression of the defective genes from a patient with delta-aminolevulinate dehydratase porphyria. J Clin Invest. 1992 May;89(5):1431-7. PMID:1569184 doi:http://dx.doi.org/10.1172/JCI115732
↑ Plewinska M, Thunell S, Holmberg L, Wetmur JG, Desnick RJ. delta-Aminolevulinate dehydratase deficient porphyria: identification of the molecular lesions in a severely affected homozygote. Am J Hum Genet. 1991 Jul;49(1):167-74. PMID:2063868
↑ Sassa S, Ishida N, Fujita H, Fukuda Y, Noguchi T, Doss M, Kappas A. Cloning and expression of the defective genes in delta-aminolevulinate dehydratase porphyria: compound heterozygosity in this hereditary liver disease. Trans Assoc Am Physicians. 1992;105:250-9. PMID:1309003
↑ Akagi R, Shimizu R, Furuyama K, Doss MO, Sassa S. Novel molecular defects of the delta-aminolevulinate dehydratase gene in a patient with inherited acute hepatic porphyria. Hepatology. 2000 Mar;31(3):704-8. PMID:10706561 doi:S0270913900700632
↑ Jaffe EK, Stith L. ALAD porphyria is a conformational disease. Am J Hum Genet. 2007 Feb;80(2):329-37. Epub 2006 Dec 21. PMID:17236137 doi:10.1086/511444
↑ Jaffe EK, Martins J, Li J, Kervinen J, Dunbrack RL Jr. The molecular mechanism of lead inhibition of human porphobilinogen synthase. J Biol Chem. 2001 Jan 12;276(2):1531-7. PMID:11032836 doi:10.1074/jbc.M007663200
↑ Lawrence SH, Ramirez UD, Selwood T, Stith L, Jaffe EK. Allosteric inhibition of human porphobilinogen synthase. J Biol Chem. 2009 Dec 18;284(51):35807-17. doi: 10.1074/jbc.M109.026294. Epub . PMID:19812033 doi:10.1074/jbc.M109.026294
↑ Breinig S, Kervinen J, Stith L, Wasson AS, Fairman R, Wlodawer A, Zdanov A, Jaffe EK. Control of tetrapyrrole biosynthesis by alternate quaternary forms of porphobilinogen synthase. Nat Struct Biol. 2003 Sep;10(9):757-63. Epub 2003 Aug 3. PMID:12897770 doi:10.1038/nsb963

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1pv8"

@@ Line 1: / Line 1: @@
 ==Crystal structure of a low activity F12L mutant of human porphobilinogen synthase==
 <StructureSection load='1pv8' size='340' side='right' caption='[[1pv8]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ALAD ([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/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></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=1pv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pv8 OCA], [http://pdbe.org/1pv8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1pv8 RCSB], [http://www.ebi.ac.uk/pdbsum/1pv8 PDBsum]</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=1pv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pv8 OCA], [http://pdbe.org/1pv8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1pv8 RCSB], [http://www.ebi.ac.uk/pdbsum/1pv8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1pv8 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 16: / Line 17: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pv/1pv8_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pv/1pv8_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 31: / Line 32: @@
 </div>
 <div class="pdbe-citations 1pv8" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Porphobilinogen synthase|Porphobilinogen synthase]]
 == References ==
 <references/>

1pv8

From Proteopedia

Revision as of 08:21, 24 February 2018

Crystal structure of a low activity F12L mutant of human porphobilinogen synthase

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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