1X9D

Crystal Structure Of Human Class I alpha-1,2-Mannosidase In Complex With Thio-Disaccharide Substrate Analogue


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.41 Å
  • R-Value Free: 0.162 
  • R-Value Work: 0.144 
  • R-Value Observed: 0.146 

wwPDB Validation   3D Report Full Report


This is version 2.1 of the entry. See complete history


Literature

Mechanism of class 1 (glycosylhydrolase family 47) {alpha}-mannosidases involved in N-glycan processing and endoplasmic reticulum quality control.

Karaveg, K.Siriwardena, A.Tempel, W.Liu, Z.J.Glushka, J.Wang, B.C.Moremen, K.W.

(2005) J Biol Chem 280: 16197-16207

  • DOI: https://doi.org/10.1074/jbc.M500119200
  • Primary Citation of Related Structures:  
    1X9D

  • PubMed Abstract: 

    Quality control in the endoplasmic reticulum (ER) determines the fate of newly synthesized glycoproteins toward either correct folding or disposal by ER-associated degradation. Initiation of the disposal process involves selective trimming of N-glycans attached to misfolded glycoproteins by ER alpha-mannosidase I and subsequent recognition by the ER degradation-enhancing alpha-mannosidase-like protein family of lectins, both members of glycosylhydrolase family 47. The unusual inverting hydrolytic mechanism catalyzed by members of this family is investigated here by a combination of kinetic and binding analyses of wild type and mutant forms of human ER alpha-mannosidase I as well as by structural analysis of a co-complex with an uncleaved thiodisaccharide substrate analog. These data reveal the roles of potential catalytic acid and base residues and the identification of a novel (3)S(1) sugar conformation for the bound substrate analog. The co-crystal structure described here, in combination with the (1)C(4) conformation of a previously identified co-complex with the glycone mimic, 1-deoxymannojirimycin, indicates that glycoside bond cleavage proceeds through a least motion conformational twist of a properly predisposed substrate in the -1 subsite. A novel (3)H(4) conformation is proposed as the exploded transition state.


  • Organizational Affiliation

    Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase538Homo sapiensMutation(s): 0 
Gene Names: MAN1B1
EC: 3.2.1.113
UniProt & NIH Common Fund Data Resources
Find proteins for Q9UKM7 (Homo sapiens)
Explore Q9UKM7 
Go to UniProtKB:  Q9UKM7
PHAROS:  Q9UKM7
GTEx:  ENSG00000177239 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9UKM7
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-2)-methyl 2-thio-alpha-D-mannopyranoside
B
2N/AN/A
Glycosylation Resources
GlyTouCan:  G32183TR
GlyCosmos:  G32183TR
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.41 Å
  • R-Value Free: 0.162 
  • R-Value Work: 0.144 
  • R-Value Observed: 0.146 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 50.687α = 89.49
b = 53.878β = 63.6
c = 56.234γ = 62.61
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
MAR345data collection
EPMRphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-02-22
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Refinement description
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Database references, Derived calculations, Non-polymer description, Structure summary
  • Version 2.1: 2023-08-23
    Changes: Data collection, Database references, Refinement description, Structure summary