2qd3: Difference between revisions
New page: left|200px<br /> <applet load="2qd3" size="450" color="white" frame="true" align="right" spinBox="true" caption="2qd3, resolution 2.20Å" /> '''Wild type human fer... |
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[[Image:2qd3.gif|left|200px]]<br /> | [[Image:2qd3.gif|left|200px]]<br /><applet load="2qd3" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="2qd3, resolution 2.20Å" /> | caption="2qd3, resolution 2.20Å" /> | ||
'''Wild type human ferrochelatase crystallized with ammonium sulfate'''<br /> | '''Wild type human ferrochelatase crystallized with ammonium sulfate'''<br /> | ||
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==Overview== | ==Overview== | ||
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. | 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 Structure== | ==About this Structure== | ||
2QD3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with FES, HEM, CHD and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | 2QD3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=FES:'>FES</scene>, <scene name='pdbligand=HEM:'>HEM</scene>, <scene name='pdbligand=CHD:'>CHD</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QD3 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: protoporphyrin ix]] | [[Category: protoporphyrin ix]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:37:22 2008'' | ||
