View source for 5kkb


==Structure of mouse Golgi alpha-1,2-mannosidase IA and Man9GlcNAc2-PA complex==
<StructureSection load='5kkb' size='340' side='right'caption='[[5kkb]], [[Resolution|resolution]] 1.77&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5kkb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KKB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KKB FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.774&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PS:3-PYRIDINIUM-1-YLPROPANE-1-SULFONATE'>1PS</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=BU1:1,4-BUTANEDIOL'>BU1</scene>, <scene name='pdbligand=LA:LANTHANUM+(III)+ION'>LA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5kkb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kkb OCA], [https://pdbe.org/5kkb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kkb RCSB], [https://www.ebi.ac.uk/pdbsum/5kkb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kkb ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MA1A1_MOUSE MA1A1_MOUSE] Involved in the maturation of Asn-linked oligosaccharides. Progressively trim alpha-1,2-linked mannose residues from Man(9)GlcNAc(2) to produce Man(5)GlcNAc(2).
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== Publication Abstract from PubMed ==
Maturation of Asn-linked oligosaccharides in the eukaryotic secretory pathway requires the trimming of nascent glycan chains to remove all glucose and several mannose residues before extension into complex-type structures on the cell surface and secreted glycoproteins. Multiple glycoside hydrolase family 47 (GH47) alpha-mannosidases, including endoplasmic reticulum (ER) alpha-mannosidase I (ERManI) and Golgi alpha-mannosidase IA (GMIA), are responsible for cleavage of terminal alpha1,2-linked mannose residues to produce uniquely trimmed oligomannose isomers that are necessary for ER glycoprotein quality control and glycan maturation. ERManI and GMIA have similar catalytic domain structures, but each enzyme cleaves distinct residues from tribranched oligomannose glycan substrates. The structural basis for branch-specific cleavage by ERManI and GMIA was explored by replacing an essential enzyme-bound Ca2+ ion with a lanthanum (La3+) ion. This ion swap led to enzyme inactivation while retaining high-affinity substrate interactions. Cocrystallization of La3+-bound enzymes with Man9GlcNAc2 substrate analogs revealed enzyme-substrate complexes with distinct modes of glycan branch insertion into the respective enzyme active-site clefts. Both enzymes had glycan interactions that extended across the entire glycan structure, but each enzyme engaged a different glycan branch and used different sets of glycan interactions. Additional mutagenesis and time-course studies of glycan cleavage probed the structural basis of enzyme specificity. The results provide insights into the enzyme catalytic mechanisms and reveal structural snapshots of the sequential glycan cleavage events. The data also indicate that full steric access to glycan substrates determines the efficiency of mannose-trimming reactions that control the conversion to complex-type structures in mammalian cells.

Substrate recognition and catalysis by GH47 alpha-mannosidases involved in Asn-linked glycan maturation in the mammalian secretory pathway.,Xiang Y, Karaveg K, Moremen KW Proc Natl Acad Sci U S A. 2016 Dec 6;113(49):E7890-E7899. Epub 2016 Nov 17. PMID:27856750<ref>PMID:27856750</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5kkb" style="background-color:#fffaf0;"></div>

==See Also==
*[[Mannosidase 3D structures|Mannosidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Moremen KW]]
[[Category: Xiang Y]]