1CB8

CHONDROITINASE AC LYASE FROM FLAVOBACTERIUM HEPARINUM

1CB8 の概要

• エントリーDOI: 10.2210/pdb1cb8/pdb
• 分子名称: PROTEIN (CHONDROITINASE AC), methyl alpha-L-fucopyranoside-(1-4)-beta-D-xylopyranose-(1-4)-alpha-D-glucopyranuronic acid-(1-2)-[alpha-L-rhamnopyranose-(1-4)]alpha-D-mannopyranose, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: lyase, chondroitin degradation
• 由来する生物種: Pedobacter heparinus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 78285.46

構造登録者

Fethiere, J.,Eggimann, B.,Cygler, M. (登録日: 1999-03-02, 公開日: 1999-05-14, 最終更新日: 2023-12-27)

主引用文献

Fethiere, J.,Eggimann, B.,Cygler, M.
Crystal structure of chondroitin AC lyase, a representative of a family of glycosaminoglycan degrading enzymes.
J.Mol.Biol., 288:635-647, 1999

PubMed Abstract: Glycosaminoglycans (GAGs), highly sulfated polymers built of hexosamine-uronic acid disaccharide units, are major components of the extracellular matrix, mostly in the form of proteoglycans. They interact with a large array of proteins, in particular of the blood coagulation cascade. Degradation of GAGs in mammalian systems occurs by the action of GAG hydrolases. Bacteria express a large number of GAG-degrading lyases that break the hexosamine-uronic acid bond to create an unsaturated sugar ring. Flavobacterium heparinum produces at least five GAG lyases of different specificity. Chondroitin AC lyase (chondroitinase AC, 75 kDa) is highly active toward chondroitin 4-sulfate and chondroitin-6 sulfate. Its crystal structure has been determined to 1.9 A resolution. The enzyme is composed of two domains. The N-terminal domain of approximately 300 residues contains mostly alpha-helices which form a doubly-layered horseshoe (a subset of the (alpha/alpha)6 toroidal topology). The approximately 370 residues long C-terminal domain is made of beta-strands arranged in a four layered beta-sheet sandwich, with the first two sheets having nine strands each. This fold is novel and has no counterpart in full among known structures. The sequence of chondroitinase AC shows low level of homology to several hyaluronate lyases, which likely share its fold. The shape of the molecule, distribution of electrostatic potential, the pattern of conservation of the amino acids and the results of mutagenesis of hyaluronate lyases, indicate that the enzymatic activity resides primarily within the N-terminal domain. The most likely candidate for the catalytic base is His225. Other residues involved in catalysis and/or substrate binding are Arg288, Arg292, Lys298 and Lys299.

PubMed: 10329169
DOI: 10.1006/jmbi.1999.2698

実験手法

X-RAY DIFFRACTION (1.9 Å)