2qd2: Difference between revisions

Revision as of 14:45, 4 May 2008

F110A variant of human ferrochelatase with protoheme bound

OverviewOverview

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.

About this StructureAbout this Structure

2QD2 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Sun May 4 14:45:21 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:2qd2.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 2qd2 |SIZE=350|CAPTION= <scene name='initialview01'>2qd2</scene>, resolution 2.20&Aring;
+The line below this paragraph, containing "STRUCTURE_2qd2", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=BCT:BICARBONATE+ION'>BCT</scene>, <scene name='pdbligand=CHD:CHOLIC+ACID'>CHD</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <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>
+or leave the SCENE parameter empty for the default display.
-|GENE= DKFZp686P18130 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_2qd2|  PDB=2qd2  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qd2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qd2 OCA], [http://www.ebi.ac.uk/pdbsum/2qd2 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2qd2 RCSB]</span>
-}}
 '''F110A variant of human ferrochelatase with protoheme bound'''
@@ Line 31: / Line 28: @@
 [[Category: Medlock, A E.]]
 [[Category: Ross, T A.]]
-[[Category: biosynthetic protein]]
+[[Category: Biosynthetic protein]]
-[[Category: ferrochelatase]]
+[[Category: Ferrochelatase]]
-[[Category: heme biosynthesis]]
+[[Category: Heme biosynthesis]]
-[[Category: heme synthesis]]
+[[Category: Heme synthesis]]
-[[Category: iron]]
+[[Category: Iron]]
-[[Category: lyase]]
+[[Category: Lyase]]
-[[Category: porphyrin biosynthesis]]
+[[Category: Porphyrin biosynthesis]]
-[[Category: protoporphyrin ix]]
+[[Category: Protoporphyrin ix]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 14:45:21 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:47:51 2008''