1nkh

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[[Image:1nkh.gif|left|200px]]<br /><applet load="1nkh" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1nkh, resolution 2.00&Aring;" />
 
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'''Crystal structure of Lactose synthase complex with UDP and Manganese'''<br />
 
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==Overview==
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==Crystal structure of Lactose synthase complex with UDP and Manganese==
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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.
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<StructureSection load='1nkh' size='340' side='right'caption='[[1nkh]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1nkh]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1j8x 1j8x]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NKH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NKH FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1nkh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nkh OCA], [https://pdbe.org/1nkh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nkh RCSB], [https://www.ebi.ac.uk/pdbsum/1nkh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nkh ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/LALBA_MOUSE LALBA_MOUSE] Regulatory subunit of lactose synthase, changes the substrate specificity of galactosyltransferase in the mammary gland making glucose a good acceptor substrate for this enzyme. This enables LS to synthesize lactose, the major carbohydrate component of milk. In other tissues, galactosyltransferase transfers galactose onto the N-acetylglucosamine of the oligosaccharide chains in glycoproteins.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nk/1nkh_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1nkh ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1NKH 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=CA:'>CA</scene>, <scene name='pdbligand=MN:'>MN</scene>, <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=UDP:'>UDP</scene> and <scene name='pdbligand=PG4:'>PG4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 1J8X. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NKH OCA].
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*[[Alpha-lactalbumin 3D structures|Alpha-lactalbumin 3D structures]]
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*[[Glycosyltransferase 3D structures|Glycosyltransferase 3D structures]]
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==Reference==
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__TOC__
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11419947 11419947]
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</StructureSection>
[[Category: Bos taurus]]
[[Category: Bos taurus]]
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Protein complex]]
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[[Category: Qasba PK]]
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[[Category: Qasba, P K.]]
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[[Category: Ramakrishnan B]]
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[[Category: Ramakrishnan, B.]]
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[[Category: CA]]
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[[Category: MN]]
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[[Category: PG4]]
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[[Category: SO4]]
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[[Category: UDP]]
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[[Category: lactose synthease]]
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[[Category: udp and mn binding]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:07:04 2008''
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Current revision

Crystal structure of Lactose synthase complex with UDP and Manganese

PDB ID 1nkh

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