Introduction

The human CBS (hCBS) is natively a homotetrameric enzyme catalysing the folowing reaction, which is part of the biosynthesis of cystein, using homocystein and serine : IMAGE It is encoded by the CBS gene located on chromosom 21.

Structure

A monomer is natively a 63kDa protein made of 551 amino-acids and each of them binds two cofactors (the iron heme and the pyridoxal phosphate), as well as two substrates (homocysteine and serine). Thus it contains (from N-terminal to C-terminal) a heme binding site, located in a hydrophobic pocket (residues 50-67), a pyridoxal phosphate binding domain (residues 256-260 which shape a β-strand) situated in a highly conserved central catalytic domain (residues 70-416) and a C-terminal regulatory domain called Bateman module, composed of two CBS domains (CBS1 and CBS2). IMAGE ALICE

Cofactor

Heme iron : The heme is one of the two cofactors of hCBS. It is bound in an hydrophobic pocket composed of the residues 50-67. The iron atom is hexacoordinated with the sulfhydryl group of Cys52 and the Nε2 atom of His65 (axial coordination) and with the four nitrogen atoms of the heme. Although the heme is essential for activity in human CBS, its role still remains an enigma. It is supposed to act as a redox sensor or as a way to facilitate a correct folding.

Pyridoxal phosphate :

This is the of the chain A of the protein.

This is the of the chain A of the protein. This is the . This is the of the protein. This is the of the protein. This is the .

Function

Disease

Relevance