1afb

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(New page: 200px<br /><applet load="1afb" size="450" color="white" frame="true" align="right" spinBox="true" caption="1afb, resolution 1.9&Aring;" /> '''STRUCTURAL BASIS OF G...)
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caption="1afb, resolution 1.9&Aring;" />
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'''STRUCTURAL BASIS OF GALACTOSE RECOGNITION IN C-TYPE ANIMAL LECTINS'''<br />
'''STRUCTURAL BASIS OF GALACTOSE RECOGNITION IN C-TYPE ANIMAL LECTINS'''<br />
==Overview==
==Overview==
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The asialoglycoprotein receptors and many other C-type (Ca2+-dependent), animal lectins specifically recognize galactose- or, N-acetylgalactosamine-terminated oligosaccharides. Analogous binding, specificity can be engineered into the homologous rat mannose-binding, protein A by changing three amino acids and inserting a glycine-rich loop, (Iobst, S. T., and Drickamer, K. (1994) J. Biol. Chem. 269, 15512-15519)., Crystal structures of this mutant complexed with beta-methyl galactoside, and N-acetylgalactosamine (GalNAc) reveal that as with wild-type, mannose-binding proteins, the 3- and 4-OH groups of the sugar directly, coordinate Ca2+ and form hydrogen bonds with amino acids that also serve, as Ca2+ ligands. The different stereochemistry of the 3- and 4-OH groups, in mannose and galactose, combined with a fixed Ca2+ coordination, geometry, leads to different pyranose ring locations in the two cases. The, glycine-rich loop provides selectivity against mannose by holding a, critical tryptophan in a position optimal for packing with the apolar face, of galactose but incompatible with mannose binding. The 2-acetamido, substituent of GalNAc is in the vicinity of amino acid positions, identified by site-directed mutagenesis (Iobst, S. T., and Drickamer, K., (1996) J. Biol. Chem. 271, 6686-6693) as being important for the formation, of a GalNAc-selective binding site.
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The asialoglycoprotein receptors and many other C-type (Ca2+-dependent) animal lectins specifically recognize galactose- or N-acetylgalactosamine-terminated oligosaccharides. Analogous binding specificity can be engineered into the homologous rat mannose-binding protein A by changing three amino acids and inserting a glycine-rich loop (Iobst, S. T., and Drickamer, K. (1994) J. Biol. Chem. 269, 15512-15519). Crystal structures of this mutant complexed with beta-methyl galactoside and N-acetylgalactosamine (GalNAc) reveal that as with wild-type mannose-binding proteins, the 3- and 4-OH groups of the sugar directly coordinate Ca2+ and form hydrogen bonds with amino acids that also serve as Ca2+ ligands. The different stereochemistry of the 3- and 4-OH groups in mannose and galactose, combined with a fixed Ca2+ coordination geometry, leads to different pyranose ring locations in the two cases. The glycine-rich loop provides selectivity against mannose by holding a critical tryptophan in a position optimal for packing with the apolar face of galactose but incompatible with mannose binding. The 2-acetamido substituent of GalNAc is in the vicinity of amino acid positions identified by site-directed mutagenesis (Iobst, S. T., and Drickamer, K. (1996) J. Biol. Chem. 271, 6686-6693) as being important for the formation of a GalNAc-selective binding site.
==About this Structure==
==About this Structure==
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1AFB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with NGA, CA and CL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1AFB OCA].
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1AFB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=NGA:'>NGA</scene>, <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AFB OCA].
==Reference==
==Reference==
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[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Kolatkar, A.R.]]
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[[Category: Kolatkar, A R.]]
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[[Category: Weis, W.I.]]
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[[Category: Weis, W I.]]
[[Category: CA]]
[[Category: CA]]
[[Category: CL]]
[[Category: CL]]
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[[Category: calcium-binding protein]]
[[Category: calcium-binding protein]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 10:48:43 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:43:52 2008''

Revision as of 09:43, 21 February 2008


1afb, resolution 1.9Å

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STRUCTURAL BASIS OF GALACTOSE RECOGNITION IN C-TYPE ANIMAL LECTINS

Overview

The asialoglycoprotein receptors and many other C-type (Ca2+-dependent) animal lectins specifically recognize galactose- or N-acetylgalactosamine-terminated oligosaccharides. Analogous binding specificity can be engineered into the homologous rat mannose-binding protein A by changing three amino acids and inserting a glycine-rich loop (Iobst, S. T., and Drickamer, K. (1994) J. Biol. Chem. 269, 15512-15519). Crystal structures of this mutant complexed with beta-methyl galactoside and N-acetylgalactosamine (GalNAc) reveal that as with wild-type mannose-binding proteins, the 3- and 4-OH groups of the sugar directly coordinate Ca2+ and form hydrogen bonds with amino acids that also serve as Ca2+ ligands. The different stereochemistry of the 3- and 4-OH groups in mannose and galactose, combined with a fixed Ca2+ coordination geometry, leads to different pyranose ring locations in the two cases. The glycine-rich loop provides selectivity against mannose by holding a critical tryptophan in a position optimal for packing with the apolar face of galactose but incompatible with mannose binding. The 2-acetamido substituent of GalNAc is in the vicinity of amino acid positions identified by site-directed mutagenesis (Iobst, S. T., and Drickamer, K. (1996) J. Biol. Chem. 271, 6686-6693) as being important for the formation of a GalNAc-selective binding site.

About this Structure

1AFB is a Single protein structure of sequence from Rattus norvegicus with , and as ligands. Full crystallographic information is available from OCA.

Reference

Structural basis of galactose recognition by C-type animal lectins., Kolatkar AR, Weis WI, J Biol Chem. 1996 Mar 22;271(12):6679-85. PMID:8636086

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