1XFB

Human Brain Fructose 1,6-(bis)phosphate Aldolase (C isozyme)

1XFB の概要

• エントリーDOI: 10.2210/pdb1xfb/pdb
• 関連するPDBエントリー: 1J4E
• 分子名称: Aldolase C (1 entity in total)
• 機能のキーワード: isozyme specificity, structural enzymology, protein-protein interactions, isozyme specific residues, structure/function, lyase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 475403.68

構造登録者

Arakaki, T.L.,Pezza, J.A.,Cronin, M.A.,Hopkins, C.E.,Zimmer, D.B.,Tolan, D.R.,Allen, K.N. (登録日: 2004-09-14, 公開日: 2005-02-08, 最終更新日: 2023-08-23)

主引用文献

Arakaki, T.L.,Pezza, J.A.,Cronin, M.A.,Hopkins, C.E.,Zimmer, D.B.,Tolan, D.R.,Allen, K.N.
Structure of human brain fructose 1,6-(bis)phosphate aldolase: linking isozyme structure with function
Protein Sci., 13:3077-3084, 2004

PubMed Abstract: 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.

PubMed: 15537755
DOI: 10.1110/ps.04915904

実験手法

X-RAY DIFFRACTION (3 Å)