1xfb
From Proteopedia
(New page: 200px<br /> <applet load="1xfb" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xfb, resolution 3.00Å" /> '''Human Brain Fructos...) |
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caption="1xfb, resolution 3.00Å" /> | caption="1xfb, resolution 3.00Å" /> | ||
'''Human Brain Fructose 1,6-(bis)phosphate Aldolase (C isozyme)'''<br /> | '''Human Brain Fructose 1,6-(bis)phosphate Aldolase (C isozyme)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Fructose-1,6-(bis)phosphate aldolase is a ubiquitous enzyme that catalyzes | + | Fructose-1,6-(bis)phosphate aldolase is a ubiquitous enzyme that catalyzes the reversible aldol cleavage of fructose-1,6-(bis)phosphate and fructose 1-phosphate to dihydroxyacetone phosphate and either glyceral-dehyde-3-phosphate or glyceraldehyde, respectively. Vertebrate aldolases exist as three isozymes with different tissue distributions and kinetics: aldolase A (muscle and red blood cell), aldolase B (liver, kidney, and small intestine), and aldolase C (brain and neuronal tissue). The structures of human aldolases A and B are known and herein we report the first structure of the human aldolase C, solved by X-ray crystallography at 3.0 A resolution. Structural differences between the isozymes were expected to account for isozyme-specific activity. However, the structures of isozymes A, B, and C are the same in their overall fold and active site structure. The subtle changes observed in active site residues Arg42, Lys146, and Arg303 are insufficient to completely account for the tissue-specific isozymic differences. Consequently, the structural analysis has been extended to the isozyme-specific residues (ISRs), those residues conserved among paralogs. A complete analysis of the ISRs in the context of this structure demonstrates that in several cases an amino acid residue that is conserved among aldolase C orthologs prevents an interaction that occurs in paralogs. In addition, the structure confirms the clustering of ISRs into discrete patches on the surface and reveals the existence in aldolase C of a patch of electronegative residues localized near the C terminus. Together, these structural changes highlight the differences required for the tissue and kinetic specificity among aldolase isozymes. |
==About this Structure== | ==About this Structure== | ||
| - | 1XFB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Fructose-bisphosphate_aldolase Fructose-bisphosphate aldolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.2.13 4.1.2.13] Full crystallographic information is available from [http:// | + | 1XFB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Fructose-bisphosphate_aldolase Fructose-bisphosphate aldolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.2.13 4.1.2.13] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XFB OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Allen, K | + | [[Category: Allen, K N.]] |
| - | [[Category: Arakaki, T | + | [[Category: Arakaki, T L.]] |
| - | [[Category: Cronin, M | + | [[Category: Cronin, M A.]] |
| - | [[Category: Hopkins, C | + | [[Category: Hopkins, C E.]] |
| - | [[Category: Pezza, J | + | [[Category: Pezza, J A.]] |
| - | [[Category: Tolan, D | + | [[Category: Tolan, D R.]] |
| - | [[Category: Zimmer, D | + | [[Category: Zimmer, D B.]] |
[[Category: isozyme specific residues]] | [[Category: isozyme specific residues]] | ||
[[Category: isozyme specificity]] | [[Category: isozyme specificity]] | ||
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[[Category: structure/function]] | [[Category: structure/function]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:54:11 2008'' |
Revision as of 13:54, 21 February 2008
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Human Brain Fructose 1,6-(bis)phosphate Aldolase (C isozyme)
Overview
Fructose-1,6-(bis)phosphate aldolase is a ubiquitous enzyme that catalyzes the reversible aldol cleavage of fructose-1,6-(bis)phosphate and fructose 1-phosphate to dihydroxyacetone phosphate and either glyceral-dehyde-3-phosphate or glyceraldehyde, respectively. Vertebrate aldolases exist as three isozymes with different tissue distributions and kinetics: aldolase A (muscle and red blood cell), aldolase B (liver, kidney, and small intestine), and aldolase C (brain and neuronal tissue). The structures of human aldolases A and B are known and herein we report the first structure of the human aldolase C, solved by X-ray crystallography at 3.0 A resolution. Structural differences between the isozymes were expected to account for isozyme-specific activity. However, the structures of isozymes A, B, and C are the same in their overall fold and active site structure. The subtle changes observed in active site residues Arg42, Lys146, and Arg303 are insufficient to completely account for the tissue-specific isozymic differences. Consequently, the structural analysis has been extended to the isozyme-specific residues (ISRs), those residues conserved among paralogs. A complete analysis of the ISRs in the context of this structure demonstrates that in several cases an amino acid residue that is conserved among aldolase C orthologs prevents an interaction that occurs in paralogs. In addition, the structure confirms the clustering of ISRs into discrete patches on the surface and reveals the existence in aldolase C of a patch of electronegative residues localized near the C terminus. Together, these structural changes highlight the differences required for the tissue and kinetic specificity among aldolase isozymes.
About this Structure
1XFB is a Single protein structure of sequence from Homo sapiens. Active as Fructose-bisphosphate aldolase, with EC number 4.1.2.13 Full crystallographic information is available from OCA.
Reference
Structure of human brain fructose 1,6-(bis)phosphate aldolase: linking isozyme structure with function., Arakaki TL, Pezza JA, Cronin MA, Hopkins CE, Zimmer DB, Tolan DR, Allen KN, Protein Sci. 2004 Dec;13(12):3077-84. Epub 2004 Nov 10. PMID:15537755
Page seeded by OCA on Thu Feb 21 15:54:11 2008
Categories: Fructose-bisphosphate aldolase | Homo sapiens | Single protein | Allen, K N. | Arakaki, T L. | Cronin, M A. | Hopkins, C E. | Pezza, J A. | Tolan, D R. | Zimmer, D B. | Isozyme specific residues | Isozyme specificity | Protein-protein interactions | Structural enzymology | Structure/function
