1o7d
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THE STRUCTURE OF THE BOVINE LYSOSOMAL A-MANNOSIDASE SUGGESTS A NOVEL MECHANISM FOR LOW PH ACTIVATION
OverviewOverview
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 StructureAbout this Structure
1O7D is a Single protein structure of sequence from Bos taurus with NAG, ZN, SO4 and TRS as ligands. Active as Alpha-mannosidase, with EC number 3.2.1.24 Structure known Active Site: ACT. Full crystallographic information is available from OCA.
ReferenceReference
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
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