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2qd5

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Revision as of 13:57, 11 September 2015

Structure of wild type human ferrochelatase in complex with a lead-porphyrin compound

Structural highlights

2qd5 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:	, , , , , ,
Related:	2qd1, 2qd3, 2qd4
Gene:	FECH (HUMAN)
Activity:	Ferrochelatase, with EC number 4.99.1.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Disease

[HEMH_HUMAN] Defects in FECH are the cause of erythropoietic protoporphyria (EPP) [MIM:177000]. 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. EPP is a form of porphyria marked by excessive protoporphyrin in erythrocytes, plasma, liver and feces, and by widely varying photosensitive skin changes ranging from a burning or pruritic sensation to erythema, edema and wheals.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12]

Function

[HEMH_HUMAN] Catalyzes the ferrous insertion into protoporphyrin IX.

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

Ferrochelatase (protoheme ferrolyase, EC 4.99.1.1) is the terminal enzyme in heme biosynthesis and catalyzes the insertion of ferrous iron into protoporphyrin IX to form protoheme IX (heme). Due to the many critical roles of heme, synthesis of heme is required by the vast majority of organisms. Despite significant investigation of both the microbial and eukaryotic enzyme, details of metal chelation remain unidentified. Here we present the first structure of the wild-type human enzyme, a lead-inhibited intermediate of the wild-type enzyme with bound metallated porphyrin macrocycle, the product bound form of the enzyme, and a higher resolution model for the substrate-bound form of the E343K variant. These data paint a picture of an enzyme that undergoes significant changes in secondary structure during the catalytic cycle. The role that these structural alterations play in overall catalysis and potential protein-protein interactions with other proteins, as well as the possible molecular basis for these changes, is discussed. The atomic details and structural rearrangements presented herein significantly advance our understanding of the substrate binding mode of ferrochelatase and reveal new conformational changes in a structurally conserved pi-helix that is predicted to have a central role in product release.

A pi-helix switch selective for porphyrin deprotonation and product release in human ferrochelatase.,Medlock AE, Dailey TA, Ross TA, Dailey HA, Lanzilotta WN J Mol Biol. 2007 Nov 2;373(4):1006-16. Epub 2007 Aug 23. PMID:17884090^[13]

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

References

↑ Lamoril J, Boulechfar S, de Verneuil H, Grandchamp B, Nordmann Y, Deybach JC. Human erythropoietic protoporphyria: two point mutations in the ferrochelatase gene. Biochem Biophys Res Commun. 1991 Dec 16;181(2):594-9. PMID:1755842
↑ Brenner DA, Didier JM, Frasier F, Christensen SR, Evans GA, Dailey HA. A molecular defect in human protoporphyria. Am J Hum Genet. 1992 Jun;50(6):1203-10. PMID:1376018
↑ Sarkany RP, Alexander GJ, Cox TM. Recessive inheritance of erythropoietic protoporphyria with liver failure. Lancet. 1994 Jun 4;343(8910):1394-6. PMID:7910885
↑ Imoto S, Tanizawa Y, Sato Y, Kaku K, Oka Y. A novel mutation in the ferrochelatase gene associated with erythropoietic protoporphyria. Br J Haematol. 1996 Jul;94(1):191-7. PMID:8757534
↑ Rufenacht UB, Gouya L, Schneider-Yin X, Puy H, Schafer BW, Aquaron R, Nordmann Y, Minder EI, Deybach JC. Systematic analysis of molecular defects in the ferrochelatase gene from patients with erythropoietic protoporphyria. Am J Hum Genet. 1998 Jun;62(6):1341-52. PMID:9585598 doi:S0002-9297(07)62775-X
↑ Gouya L, Schneider-Yin X, Rufenacht U, Herrero C, Lecha M, Mascaro JM, Puy H, Deybach JC, Minder EI. Mutations in the ferrochelatase gene of four Spanish patients with erythropoietic protoporphyria. J Invest Dermatol. 1998 Sep;111(3):406-9. PMID:9740232 doi:10.1046/j.1523-1747.1998.00327.x
↑ Schneider-Yin X, Gouya L, Dorsey M, Rufenacht U, Deybach JC, Ferreira GC. Mutations in the iron-sulfur cluster ligands of the human ferrochelatase lead to erythropoietic protoporphyria. Blood. 2000 Aug 15;96(4):1545-9. PMID:10942404
↑ Rufenacht UB, Gregor A, Gouya L, Tarczynska-Nosal S, Schneider-Yin X, Deybach JC. New missense mutation in the human ferrochelatase gene in a family with erythropoietic protoporphyria: functional studies and correlation of genotype and phenotype. Clin Chem. 2001 Jun;47(6):1112-3. PMID:11375302
↑ Poh-Fitzpatrick MB, Wang X, Anderson KE, Bloomer JR, Bolwell B, Lichtin AE. Erythropoietic protoporphyria: altered phenotype after bone marrow transplantation for myelogenous leukemia in a patient heteroallelic for ferrochelatase gene mutations. J Am Acad Dermatol. 2002 Jun;46(6):861-6. PMID:12063482
↑ Wiman A, Floderus Y, Harper P. Novel mutations and phenotypic effect of the splice site modulator IVS3-48C in nine Swedish families with erythropoietic protoporphyria. J Hum Genet. 2003;48(2):70-6. PMID:12601550 doi:10.1007/s100380300009
↑ Whatley SD, Mason NG, Khan M, Zamiri M, Badminton MN, Missaoui WN, Dailey TA, Dailey HA, Douglas WS, Wainwright NJ, Elder GH. Autosomal recessive erythropoietic protoporphyria in the United Kingdom: prevalence and relationship to liver disease. J Med Genet. 2004 Aug;41(8):e105. PMID:15286165 doi:10.1136/jmg.2003.016121
↑ Aurizi C, Schneider-Yin X, Sorge F, Macri A, Minder EI, Biolcati G. Heterogeneity of mutations in the ferrochelatase gene in Italian patients with erythropoietic protoporphyria. Mol Genet Metab. 2007 Apr;90(4):402-7. Epub 2006 Dec 29. PMID:17196862 doi:S1096-7192(06)00355-6
↑ Medlock AE, Dailey TA, Ross TA, Dailey HA, Lanzilotta WN. A pi-helix switch selective for porphyrin deprotonation and product release in human ferrochelatase. J Mol Biol. 2007 Nov 2;373(4):1006-16. Epub 2007 Aug 23. PMID:17884090 doi:10.1016/j.jmb.2007.08.040

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2qd5"

@@ Line 2: / Line 2: @@
 <StructureSection load='2qd5' size='340' side='right' caption='[[2qd5]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2qd5]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QD5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QD5 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2qd5]] 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=2QD5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QD5 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=CHD:CHOLIC+ACID'>CHD</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=OXY:OXYGEN+MOLECULE'>OXY</scene>, <scene name='pdbligand=PB:LEAD+(II)+ION'>PB</scene>, <scene name='pdbligand=PP9:PROTOPORPHYRIN+IX'>PP9</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2qd1|2qd1]], [[2qd3|2qd3]], [[2qd4|2qd4]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FECH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FECH ([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/Ferrochelatase Ferrochelatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.99.1.1 4.99.1.1] </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=2qd5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qd5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2qd5 RCSB], [http://www.ebi.ac.uk/pdbsum/2qd5 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=2qd5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qd5 OCA], [http://pdbe.org/2qd5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qd5 RCSB], [http://www.ebi.ac.uk/pdbsum/2qd5 PDBsum]</span></td></tr>
 </table>
 == Disease ==
@@ Line 31: / Line 31: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2qd5" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 39: / Line 40: @@
 </StructureSection>
 [[Category: Ferrochelatase]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Dailey, H A]]
 [[Category: Dailey, T A]]

2qd5

From Proteopedia

Revision as of 13:57, 11 September 2015

Structure of wild type human ferrochelatase in complex with a lead-porphyrin compound

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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