2hrc

From Proteopedia

(Difference between revisions)

Current revision

1.7 angstrom structure of human ferrochelatase variant R115L

Structural highlights

2hrc is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.7Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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, the terminal enzyme in heme biosynthesis, catalyzes the insertion of ferrous iron into protoporphyrin IX to form protoheme IX. Human ferrochelatase is a homodimeric, inner mitochondrial membrane-associated enzyme that possesses an essential [2Fe-2S] cluster. In this work, we report the crystal structure of human ferrochelatase with the substrate protoporphyrin IX bound as well as a higher resolution structure of the R115L variant without bound substrate. The data presented reveal that the porphyrin substrate is bound deep within an enclosed pocket. When compared with the location of N-methylmesoporphyrin in the Bacillus subtilis ferrochelatase, the porphyrin is rotated by approximately 100 degrees and is buried an additional 4.5 A deeper within the active site. The propionate groups of the substrate do not protrude into solvent and are bound in a manner similar to what has been observed in uroporphyrinogen decarboxylase. Furthermore, in the substrate-bound form, the jaws of the active site mouth are closed so that the porphyrin substrate is completely engulfed in the pocket. These data provide insights that will aid in the determination of the mechanism for ferrochelatase.

Substrate interactions with human ferrochelatase.,Medlock A, Swartz L, Dailey TA, Dailey HA, Lanzilotta WN Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1789-93. Epub 2007 Jan 29. PMID:17261801^[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 A, Swartz L, Dailey TA, Dailey HA, Lanzilotta WN. Substrate interactions with human ferrochelatase. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1789-93. Epub 2007 Jan 29. PMID:17261801

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/2hrc"

@@ Line 1: / Line 1: @@
 ==1.7 angstrom structure of human ferrochelatase variant R115L==
-<StructureSection load='2hrc' size='340' side='right' caption='[[2hrc]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+<StructureSection load='2hrc' size='340' side='right'caption='[[2hrc]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2hrc]] 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=2HRC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HRC FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2hrc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HRC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HRC FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CHD:CHOLIC+ACID'>CHD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</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]] 1.7&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2hre|2hre]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CHD:CHOLIC+ACID'>CHD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2hrc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hrc OCA], [https://pdbe.org/2hrc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hrc RCSB], [https://www.ebi.ac.uk/pdbsum/2hrc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hrc ProSAT]</span></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=2hrc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hrc OCA], [http://pdbe.org/2hrc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hrc RCSB], [http://www.ebi.ac.uk/pdbsum/2hrc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2hrc ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/HEMH_HUMAN HEMH_HUMAN]] Defects in FECH are the cause of erythropoietic protoporphyria (EPP) [MIM:[http://omim.org/entry/177000 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.<ref>PMID:1755842</ref> <ref>PMID:1376018</ref> <ref>PMID:7910885</ref> <ref>PMID:8757534</ref> <ref>PMID:9585598</ref> <ref>PMID:9740232</ref> <ref>PMID:10942404</ref> <ref>PMID:11375302</ref> <ref>PMID:12063482</ref> <ref>PMID:12601550</ref> <ref>PMID:15286165</ref> <ref>PMID:17196862</ref>
+[https://www.uniprot.org/uniprot/HEMH_HUMAN HEMH_HUMAN] Defects in FECH are the cause of erythropoietic protoporphyria (EPP) [MIM:[https://omim.org/entry/177000 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.<ref>PMID:1755842</ref> <ref>PMID:1376018</ref> <ref>PMID:7910885</ref> <ref>PMID:8757534</ref> <ref>PMID:9585598</ref> <ref>PMID:9740232</ref> <ref>PMID:10942404</ref> <ref>PMID:11375302</ref> <ref>PMID:12063482</ref> <ref>PMID:12601550</ref> <ref>PMID:15286165</ref> <ref>PMID:17196862</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/HEMH_HUMAN HEMH_HUMAN]] Catalyzes the ferrous insertion into protoporphyrin IX.
+[https://www.uniprot.org/uniprot/HEMH_HUMAN HEMH_HUMAN] Catalyzes the ferrous insertion into protoporphyrin IX.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 35: / Line 33: @@
 ==See Also==
-*[[Ferrochelatase|Ferrochelatase]]
+*[[Ferrochelatase 3D structures|Ferrochelatase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Ferrochelatase]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
+[[Category: Large Structures]]
-[[Category: Dailey, H A]]
+[[Category: Dailey HA]]
-[[Category: Dailey, T A]]
+[[Category: Dailey TA]]
-[[Category: Lanzilotta, W N]]
+[[Category: Lanzilotta WN]]
-[[Category: Medlock, A]]
+[[Category: Medlock A]]
-[[Category: Swartz, L]]
+[[Category: Swartz L]]
-[[Category: Heme synthesis]]
-[[Category: Lyase]]
-[[Category: Protoporphyrin ix]]

2hrc

From Proteopedia

Current revision

1.7 angstrom structure of human ferrochelatase variant R115L

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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