1r3w: Difference between revisions
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|PDB= 1r3w |SIZE=350|CAPTION= <scene name='initialview01'>1r3w</scene>, resolution 1.70Å | |PDB= 1r3w |SIZE=350|CAPTION= <scene name='initialview01'>1r3w</scene>, resolution 1.70Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=CP3:COPROPORPHYRIN III'>CP3</scene> | |LIGAND= <scene name='pdbligand=CP3:COPROPORPHYRIN+III'>CP3</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Uroporphyrinogen_decarboxylase Uroporphyrinogen decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.37 4.1.1.37] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Uroporphyrinogen_decarboxylase Uroporphyrinogen decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.37 4.1.1.37] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1uro|1URO]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1r3w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r3w OCA], [http://www.ebi.ac.uk/pdbsum/1r3w PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1r3w RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
Uroporphyrinogen decarboxylase (URO-D), an essential enzyme that functions in the heme biosynthetic pathway, catalyzes decarboxylation of all four acetate groups of uroporphyrinogen to form coproporphyrinogen. Here we report crystal structures of URO-D in complex with the I and III isomer coproporphyrinogen products. Crystallization required use of a novel enzymatic approach to generate the highly oxygen-sensitive porphyrinogen substrate in situ. The tetrapyrrole product adopts a domed conformation that lies against a collar of conserved hydrophobic residues and allows formation of hydrogen bonding interactions between a carboxylate oxygen atom of the invariant Asp86 residue and the pyrrole NH groups. Structural and biochemical analyses of URO-D proteins mutated at Asp86 support the conclusion that this residue makes important contributions to binding and likely promotes catalysis by stabilizing a positive charge on a reaction intermediate. The central coordination geometry of Asp86 allows the initial substrates and the various partially decarboxylated intermediates to be bound with equivalent activating interactions, and thereby explains how all four of the substrate acetate groups can be decarboxylated at the same catalytic center. | Uroporphyrinogen decarboxylase (URO-D), an essential enzyme that functions in the heme biosynthetic pathway, catalyzes decarboxylation of all four acetate groups of uroporphyrinogen to form coproporphyrinogen. Here we report crystal structures of URO-D in complex with the I and III isomer coproporphyrinogen products. Crystallization required use of a novel enzymatic approach to generate the highly oxygen-sensitive porphyrinogen substrate in situ. The tetrapyrrole product adopts a domed conformation that lies against a collar of conserved hydrophobic residues and allows formation of hydrogen bonding interactions between a carboxylate oxygen atom of the invariant Asp86 residue and the pyrrole NH groups. Structural and biochemical analyses of URO-D proteins mutated at Asp86 support the conclusion that this residue makes important contributions to binding and likely promotes catalysis by stabilizing a positive charge on a reaction intermediate. The central coordination geometry of Asp86 allows the initial substrates and the various partially decarboxylated intermediates to be bound with equivalent activating interactions, and thereby explains how all four of the substrate acetate groups can be decarboxylated at the same catalytic center. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Phillips, J D.]] | [[Category: Phillips, J D.]] | ||
[[Category: Whitby, F G.]] | [[Category: Whitby, F G.]] | ||
[[Category: | [[Category: uroporphyrinogen decarboxylase coproporphyrinogen]] | ||
[[Category: | [[Category: x-ray crystallography]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:22:52 2008'' | ||
Revision as of 23:22, 30 March 2008
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| , resolution 1.70Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | Uroporphyrinogen decarboxylase, with EC number 4.1.1.37 | ||||||
| Related: | 1URO
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Uroporphyrinogen Decarboxylase Y164F mutant in complex with coproporphyrinogen-III
OverviewOverview
Uroporphyrinogen decarboxylase (URO-D), an essential enzyme that functions in the heme biosynthetic pathway, catalyzes decarboxylation of all four acetate groups of uroporphyrinogen to form coproporphyrinogen. Here we report crystal structures of URO-D in complex with the I and III isomer coproporphyrinogen products. Crystallization required use of a novel enzymatic approach to generate the highly oxygen-sensitive porphyrinogen substrate in situ. The tetrapyrrole product adopts a domed conformation that lies against a collar of conserved hydrophobic residues and allows formation of hydrogen bonding interactions between a carboxylate oxygen atom of the invariant Asp86 residue and the pyrrole NH groups. Structural and biochemical analyses of URO-D proteins mutated at Asp86 support the conclusion that this residue makes important contributions to binding and likely promotes catalysis by stabilizing a positive charge on a reaction intermediate. The central coordination geometry of Asp86 allows the initial substrates and the various partially decarboxylated intermediates to be bound with equivalent activating interactions, and thereby explains how all four of the substrate acetate groups can be decarboxylated at the same catalytic center.
About this StructureAbout this Structure
1R3W is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for tetrapyrrole coordination by uroporphyrinogen decarboxylase., Phillips JD, Whitby FG, Kushner JP, Hill CP, EMBO J. 2003 Dec 1;22(23):6225-33. PMID:14633982
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