1o7d: Difference between revisions
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==Overview== | ==Overview== | ||
Lysosomal alpha-mannosidase (LAM: EC 3.2.1.24) belongs to the | 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== | ==About this Structure== | ||
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[[Category: Hough, E.]] | [[Category: Hough, E.]] | ||
[[Category: Karlsen, S.]] | [[Category: Karlsen, S.]] | ||
[[Category: Leiros, H | [[Category: Leiros, H S.]] | ||
[[Category: Leiros, I.]] | [[Category: Leiros, I.]] | ||
[[Category: Mcsweeney, S.]] | [[Category: Mcsweeney, S.]] | ||
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[[Category: Ruigrok, R.]] | [[Category: Ruigrok, R.]] | ||
[[Category: Schoehn, G.]] | [[Category: Schoehn, G.]] | ||
[[Category: Tollersrud, O | [[Category: Tollersrud, O K.]] | ||
[[Category: NAG]] | [[Category: NAG]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
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[[Category: lysosomal]] | [[Category: lysosomal]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:14:23 2008'' | ||
Revision as of 12:14, 21 February 2008
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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 NAG, ZN, SO4 and TRS as ligands. Active as Alpha-mannosidase, with EC number 3.2.1.24 Known structural/functional Site: ACT. 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
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