This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


1fmi

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (11:14, 27 March 2024) (edit) (undo)
 
(16 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1fmi.gif|left|200px]]<br /><applet load="1fmi" size="350" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1fmi, resolution 1.90&Aring;" />
 
-
'''CRYSTAL STRUCTURE OF HUMAN CLASS I ALPHA1,2-MANNOSIDASE'''<br />
 
-
==Overview==
+
==CRYSTAL STRUCTURE OF HUMAN CLASS I ALPHA1,2-MANNOSIDASE==
-
Endoplasmic reticulum (ER) class I alpha1,2-mannosidase (also known as ER alpha-mannosidase I) is a critical enzyme in the maturation of N-linked oligosaccharides and ER-associated degradation. Trimming of a single mannose residue acts as a signal to target misfolded glycoproteins for degradation by the proteasome. Crystal structures of the catalytic domain of human ER class I alpha1,2-mannosidase have been determined both in the presence and absence of the potent inhibitors kifunensine and 1-deoxymannojirimycin. Both inhibitors bind to the protein at the bottom of the active-site cavity, with the essential calcium ion coordinating the O-2' and O-3' hydroxyls and stabilizing the six-membered rings of both inhibitors in a (1)C(4) conformation. This is the first direct evidence of the role of the calcium ion. The lack of major conformational changes upon inhibitor binding and structural comparisons with the yeast alpha1, 2-mannosidase enzyme-product complex suggest that this class of inverting enzymes has a novel catalytic mechanism. The structures also provide insight into the specificity of this class of enzymes and provide a blueprint for the future design of novel inhibitors that prevent degradation of misfolded proteins in genetic diseases.
+
<StructureSection load='1fmi' size='340' side='right'caption='[[1fmi]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1fmi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FMI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FMI 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]] 1.9&#8491;</td></tr>
 +
<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=SO4:SULFATE+ION'>SO4</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=1fmi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fmi OCA], [https://pdbe.org/1fmi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fmi RCSB], [https://www.ebi.ac.uk/pdbsum/1fmi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fmi ProSAT]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[https://www.uniprot.org/uniprot/MA1B1_HUMAN MA1B1_HUMAN] Defects in MAN1B1 are the cause of mental retardation autosomal recessive type 15 (MRT15) [MIM:[https://omim.org/entry/614202 614202]. Mental retardation is characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period.<ref>PMID:21763484</ref>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/MA1B1_HUMAN MA1B1_HUMAN] Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc(2), but at high enzyme concentrations, as found in the ER quality control compartment (ERQC), it further trims the carbohydrates to Man(5-6)GlcNAc(2).<ref>PMID:12090241</ref> <ref>PMID:18003979</ref>
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fm/1fmi_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</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=1fmi ConSurf].
 +
<div style="clear:both"></div>
-
==About this Structure==
+
==See Also==
-
1FMI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Mannosyl-oligosaccharide_1,2-alpha-mannosidase Mannosyl-oligosaccharide 1,2-alpha-mannosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.113 3.2.1.113] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FMI OCA].
+
*[[Mannosidase 3D structures|Mannosidase 3D structures]]
-
 
+
== References ==
-
==Reference==
+
<references/>
-
Structural basis for catalysis and inhibition of N-glycan processing class I alpha 1,2-mannosidases., Vallee F, Karaveg K, Herscovics A, Moremen KW, Howell PL, J Biol Chem. 2000 Dec 29;275(52):41287-98. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10995765 10995765]
+
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Mannosyl-oligosaccharide 1,2-alpha-mannosidase]]
+
[[Category: Large Structures]]
-
[[Category: Single protein]]
+
[[Category: Herscovics A]]
-
[[Category: Herscovics, A.]]
+
[[Category: Howell PL]]
-
[[Category: Howell, P L.]]
+
[[Category: Karaveg K]]
-
[[Category: Karaveg, K.]]
+
[[Category: Moremen KW]]
-
[[Category: Moremen, K W.]]
+
[[Category: Vallee F]]
-
[[Category: Vallee, F.]]
+
-
[[Category: CA]]
+
-
[[Category: SO4]]
+
-
[[Category: alpha-alpha7 barrel]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:40:15 2008''
+

Current revision

CRYSTAL STRUCTURE OF HUMAN CLASS I ALPHA1,2-MANNOSIDASE

PDB ID 1fmi

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1fmi"
Personal tools