1r3w: Difference between revisions
New page: left|200px<br /> <applet load="1r3w" size="450" color="white" frame="true" align="right" spinBox="true" caption="1r3w, resolution 1.70Å" /> '''Uroporphyrinogen De... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1r3w.gif|left|200px]]<br /> | [[Image:1r3w.gif|left|200px]]<br /><applet load="1r3w" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1r3w" size=" | |||
caption="1r3w, resolution 1.70Å" /> | caption="1r3w, resolution 1.70Å" /> | ||
'''Uroporphyrinogen Decarboxylase Y164F mutant in complex with coproporphyrinogen-III'''<br /> | '''Uroporphyrinogen Decarboxylase Y164F mutant in complex with coproporphyrinogen-III'''<br /> | ||
==Overview== | ==Overview== | ||
Uroporphyrinogen decarboxylase (URO-D), an essential enzyme that functions | 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. | ||
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
1R3W 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 CP3 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http:// | 1R3W 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=CP3:'>CP3</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R3W OCA]. | ||
==Reference== | ==Reference== | ||
| Line 18: | Line 17: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Uroporphyrinogen decarboxylase]] | [[Category: Uroporphyrinogen decarboxylase]] | ||
[[Category: Hill, C | [[Category: Hill, C P.]] | ||
[[Category: Kushner, J | [[Category: Kushner, J P.]] | ||
[[Category: Phillips, J | [[Category: Phillips, J D.]] | ||
[[Category: Whitby, F | [[Category: Whitby, F G.]] | ||
[[Category: CP3]] | [[Category: CP3]] | ||
[[Category: uroporphyrinogen decarboxylase coproporphyrinogen; x-ray crystallography]] | [[Category: uroporphyrinogen decarboxylase coproporphyrinogen; x-ray crystallography]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:46:49 2008'' | ||
Revision as of 15:46, 21 February 2008
|
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.
DiseaseDisease
Known diseases associated with this structure: Porphyria cutanea tarda OMIM:[176100], Porphyria, hepatoerythropoietic OMIM:[176100]
About this StructureAbout this Structure
1R3W is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Uroporphyrinogen decarboxylase, with EC number 4.1.1.37 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
Page seeded by OCA on Thu Feb 21 14:46:49 2008