1o7d

From Proteopedia

Revision as of 12:14, 21 February 2008

THE STRUCTURE OF THE BOVINE LYSOSOMAL A-MANNOSIDASE SUGGESTS A NOVEL MECHANISM FOR LOW PH ACTIVATION

Overview

Lysosomal alpha-mannosidase (LAM: EC 3.2.1.24) belongs to the sequence-based glycoside hydrolase family 38 (GH38). Two other mammalian GH38 members, Golgi alpha-mannosidase II (GIIAM) and cytosolic alpha-mannosidase, are expressed in all tissues. In humans, cattle, cat and guinea pig, lack of lysosomal alpha-mannosidase activity causes the autosomal recessive disease alpha-mannosidosis. Here, we describe the three-dimensional structure of bovine lysosomal alpha-mannosidase (bLAM) at 2.7A resolution and confirm the solution state dimer by electron microscopy. We present the first structure of a mammalian GH38 enzyme that offers indications for the signal areas for mannose phosphorylation, suggests a previously undetected mechanism of low-pH activation and provides a template for further biochemical studies of the family 38 glycoside hydrolases as well as lysosomal transport. Furthermore, it provides a basis for understanding the human form of alpha-mannosidosis at the atomic level. The atomic coordinates and structure factors have been deposited in the Protein Data Bank (accession codes 1o7d and r1o7dsf).

About this Structure

1O7D is a Single protein structure of sequence from Bos taurus with , , and as ligands. Active as Alpha-mannosidase, with EC number 3.2.1.24 Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

The structure of bovine lysosomal alpha-mannosidase suggests a novel mechanism for low-pH activation., Heikinheimo P, Helland R, Leiros HK, Leiros I, Karlsen S, Evjen G, Ravelli R, Schoehn G, Ruigrok R, Tollersrud OK, McSweeney S, Hough E, J Mol Biol. 2003 Mar 28;327(3):631-44. PMID:12634058

Page seeded by OCA on Thu Feb 21 14:14:23 2008