1O7D: The Structure of the Bovine Lysosomal A-mannosidase Suggests a Novel Mechanism for LOW PH Activation

Citation:
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).
PDB ID: 1O7DDownload
MMDB ID: 22470
PDB Deposition Date: 2002/10/30
Updated in MMDB: 2007/10 
Experimental Method:
x-ray diffraction
Resolution: 2.7  Å
Source Organism:
Similar Structures:
Biological Unit for 1O7D: pentameric; determined by author and by software (PQS)
Molecular Components in 1O7D
Label Count Molecule
Proteins (5 molecules)
1
Lysosomal Alpha-mannosidase(Gene symbol: MAN2B1)
Molecule annotation
1
Lysosomal Alpha-mannosidase(Gene symbol: MAN2B1)
Molecule annotation
1
Lysosomal Alpha-mannosidase(Gene symbol: MAN2B1)
Molecule annotation
1
Lysosomal Alpha-mannosidase(Gene symbol: MAN2B1)
Molecule annotation
1
Lysosomal Alpha-mannosidase(Gene symbol: MAN2B1)
Molecule annotation
Chemicals (20 molecules)
1
7
2
1
3
1
4
2
5
2
6
1
7
6
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.