2qd3: Difference between revisions

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[[Image:2qd3.gif|left|200px]]
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{{STRUCTURE_2qd3|  PDB=2qd3  |  SCENE=  }}  
{{STRUCTURE_2qd3|  PDB=2qd3  |  SCENE=  }}  


'''Wild type human ferrochelatase crystallized with ammonium sulfate'''
===Wild type human ferrochelatase crystallized with ammonium sulfate===




==Overview==
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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.
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{{ABSTRACT_PUBMED_17884090}}


==Disease==
==Disease==
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[[Category: Lyase]]
[[Category: Lyase]]
[[Category: Protoporphyrin ix]]
[[Category: Protoporphyrin ix]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 14:45:29 2008''
 
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Revision as of 18:21, 27 July 2008

File:2qd3.png

Template:STRUCTURE 2qd3

Wild type human ferrochelatase crystallized with ammonium sulfateWild type human ferrochelatase crystallized with ammonium sulfate

Template:ABSTRACT PUBMED 17884090

DiseaseDisease

Known disease associated with this structure: Protoporphyria, erythropoietic OMIM:[177000], Protoporphyria, erythropoietic, recessive, with liver failure OMIM:[177000]

About this StructureAbout this Structure

2QD3 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

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