1nf5
From Proteopedia
(New page: 200px<br /><applet load="1nf5" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nf5, resolution 2.00Å" /> '''Crystal Structure of...) |
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| - | [[Image:1nf5.gif|left|200px]]<br /><applet load="1nf5" size=" | + | [[Image:1nf5.gif|left|200px]]<br /><applet load="1nf5" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1nf5, resolution 2.00Å" /> | caption="1nf5, resolution 2.00Å" /> | ||
'''Crystal Structure of Lactose Synthase, Complex with Glucose'''<br /> | '''Crystal Structure of Lactose Synthase, Complex with Glucose'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The lactose synthase (LS) enzyme is a 1:1 complex of a catalytic | + | The lactose synthase (LS) enzyme is a 1:1 complex of a catalytic component, beta1,4-galactosyltransferse (beta4Gal-T1) and a regulatory component, alpha-lactalbumin (LA), a mammary gland-specific protein. LA promotes the binding of glucose (Glc) to beta4Gal-T1, thereby altering its sugar acceptor specificity from N-acetylglucosamine (GlcNAc) to glucose, which enables LS to synthesize lactose, the major carbohydrate component of milk. The crystal structures of LS bound with various substrates were solved at 2 A resolution. These structures reveal that upon substrate binding to beta4Gal-T1, a large conformational change occurs in the region comprising residues 345 to 365. This repositions His347 in such a way that it can participate in the coordination of a metal ion, and creates a sugar and LA-binding site. At the sugar-acceptor binding site, a hydrophobic N-acetyl group-binding pocket is found, formed by residues Arg359, Phe360 and Ile363. In the Glc-bound structure, this hydrophobic pocket is absent. For the binding of Glc to LS, a reorientation of the Arg359 side-chain occurs, which blocks the hydrophobic pocket and maximizes the interactions with the Glc molecule. Thus, the role of LA is to hold Glc by hydrogen bonding with the O-1 hydroxyl group in the acceptor-binding site on beta4Gal-T1, while the N-acetyl group-binding pocket in beta4Gal-T1 adjusts to maximize the interactions with the Glc molecule. This study provides details of a structural basis for the partially ordered kinetic mechanism proposed for lactose synthase. |
==About this Structure== | ==About this Structure== | ||
| - | 1NF5 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with GLC, CA, PG4 and EDO as [http://en.wikipedia.org/wiki/ligands ligands]. This structure | + | 1NF5 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=GLC:'>GLC</scene>, <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=PG4:'>PG4</scene> and <scene name='pdbligand=EDO:'>EDO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 1J8W. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NF5 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Qasba, P | + | [[Category: Qasba, P K.]] |
[[Category: Ramakrishnan, B.]] | [[Category: Ramakrishnan, B.]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: transferase modulator]] | [[Category: transferase modulator]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:05:25 2008'' |
Revision as of 12:05, 21 February 2008
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Crystal Structure of Lactose Synthase, Complex with Glucose
Overview
The lactose synthase (LS) enzyme is a 1:1 complex of a catalytic component, beta1,4-galactosyltransferse (beta4Gal-T1) and a regulatory component, alpha-lactalbumin (LA), a mammary gland-specific protein. LA promotes the binding of glucose (Glc) to beta4Gal-T1, thereby altering its sugar acceptor specificity from N-acetylglucosamine (GlcNAc) to glucose, which enables LS to synthesize lactose, the major carbohydrate component of milk. The crystal structures of LS bound with various substrates were solved at 2 A resolution. These structures reveal that upon substrate binding to beta4Gal-T1, a large conformational change occurs in the region comprising residues 345 to 365. This repositions His347 in such a way that it can participate in the coordination of a metal ion, and creates a sugar and LA-binding site. At the sugar-acceptor binding site, a hydrophobic N-acetyl group-binding pocket is found, formed by residues Arg359, Phe360 and Ile363. In the Glc-bound structure, this hydrophobic pocket is absent. For the binding of Glc to LS, a reorientation of the Arg359 side-chain occurs, which blocks the hydrophobic pocket and maximizes the interactions with the Glc molecule. Thus, the role of LA is to hold Glc by hydrogen bonding with the O-1 hydroxyl group in the acceptor-binding site on beta4Gal-T1, while the N-acetyl group-binding pocket in beta4Gal-T1 adjusts to maximize the interactions with the Glc molecule. This study provides details of a structural basis for the partially ordered kinetic mechanism proposed for lactose synthase.
About this Structure
1NF5 is a Protein complex structure of sequences from Bos taurus and Mus musculus with , , and as ligands. This structure supersedes the now removed PDB entry 1J8W. Full crystallographic information is available from OCA.
Reference
Crystal structure of lactose synthase reveals a large conformational change in its catalytic component, the beta1,4-galactosyltransferase-I., Ramakrishnan B, Qasba PK, J Mol Biol. 2001 Jun 29;310(1):205-18. PMID:11419947
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