1O7D

The structure of the bovine lysosomal a-mannosidase suggests a novel mechanism for low pH activation

Summary for 1O7D

• Entry DOI: 10.2210/pdb1o7d/pdb
• Descriptor: Lysosomal alpha-mannosidase, ZINC ION, SULFATE ION, ... (12 entities in total)
• Functional Keywords: hydrolase, glycosyl hydrolase family 38, a-mannosidase, lysosomal
• Biological source: Bos taurus (Bovine); More
• Total number of polymer chains: 5
• Total formula weight: 111487.00

Authors

Heikinheimo, P.,Helland, R.,Leiros, H.S.,Leiros, I.,Karlsen, S.,Evjen, G.,Ravelli, R.,Schoehn, G.,Ruigrok, R.,Tollersrud, O.-K.,Mcsweeney, S.,Hough, E. (deposition date: 2002-10-30, release date: 2003-03-20, Last modification date: 2024-10-09)

Primary citation

Heikinheimo, P.,Helland, R.,Leiros, H.S.,Leiros, I.,Karlsen, S.,Evjen, G.,Ravelli, R.,Schoehn, G.,Ruigrok, R.,Tollersrud, O.-K.,Mcsweeney, S.,Hough, E.
The Structure of Bovine Lysosomal Alpha-Mannosidase Suggests a Novel Mechanism for Low-Ph Activation
J.Mol.Biol., 327:631-, 2003

PubMed Abstract: 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).

PubMed: 12634058
DOI: 10.1016/S0022-2836(03)00172-4

Experimental method

X-RAY DIFFRACTION (2.7 Å)