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Modulation of activity by Arg407: structure of a fungal alpha-1,2-mannosidase in complex with a substrate analogue

Yuri Lobsanov, Takashi Yoshida, Tom Desmet UGent, Wim Nerinckx UGent, Patrick Yip, Marc Claeyssens, Annette Herscovics and Lynne Howell (2008) ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY. 64(3). p.227-236
abstract
Class I alpha-mannosidases ( glycoside hydrolase family GH47) play key roles in the maturation of N-glycans and the ER-associated degradation of unfolded glycoproteins. The 1.95 angstrom resolution structure of a fungal alpha-1,2-mannosidase in complex with the substrate analogue methyl-alpha-D-lyxopyranosyl-(1 ',2)-alpha-D-mannopyranoside (LM) shows the intact disaccharide spanning the -1/+1 subsites, with the D-lyxoside ring in the -1 subsite in the C-1(4) chair conformation, and provides insight into the mechanism of catalysis. The absence of the C5 ' hydroxymethyl group on the D-lyxoside moiety results in the side chain of Arg407 adopting two alternative conformations: the minor one interacting with Asp375 and the major one interacting with both the D-lyxoside and the catalytic base Glu409, thus disrupting its function. Chemical modification of Asp375 has previously been shown to inactivate the enzyme. Taken together, the data suggest that Arg407, which belongs to the conserved sequence motif RPExxE, may act to modulate the activity of the enzyme. The proposed mechanism for modulating the activity is potentially a general mechanism for this superfamily.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
ER-ASSOCIATED DEGRADATION, RETICULUM-ASSOCIATED DEGRADATION, MANNOSIDASE-LIKE PROTEIN, CLASS-I ALPHA-1, 2-MANNOSIDASES, N-GLYCAN BIOSYNTHESIS, ENDOPLASMIC-RETICULUM, ALPHA-MANNOSIDASE, QUALITY-CONTROL, SACCHAROMYCES-CEREVISIAE, GLYCOPROTEIN-BIOSYNTHESIS
journal title
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
Acta Crystallogr. Sect. D-Biol. Crystallogr.
volume
64
issue
3
pages
227 - 236
Web of Science type
Article
Web of Science id
000253427100001
JCR category
CRYSTALLOGRAPHY
JCR impact factor
2.943 (2008)
JCR rank
4/25 (2008)
JCR quartile
1 (2008)
ISSN
0907-4449
DOI
10.1107/S0907444907065572
language
English
UGent publication?
yes
classification
A1
id
414553
handle
http://hdl.handle.net/1854/LU-414553
date created
2008-05-15 09:47:00
date last changed
2016-12-19 15:43:13
@article{414553,
  abstract     = {Class I alpha-mannosidases ( glycoside hydrolase family GH47) play key roles in the maturation of N-glycans and the ER-associated degradation of unfolded glycoproteins. The 1.95 angstrom resolution structure of a fungal alpha-1,2-mannosidase in complex with the substrate analogue methyl-alpha-D-lyxopyranosyl-(1 ',2)-alpha-D-mannopyranoside (LM) shows the intact disaccharide spanning the -1/+1 subsites, with the D-lyxoside ring in the -1 subsite in the C-1(4) chair conformation, and provides insight into the mechanism of catalysis. The absence of the C5 ' hydroxymethyl group on the D-lyxoside moiety results in the side chain of Arg407 adopting two alternative conformations: the minor one interacting with Asp375 and the major one interacting with both the D-lyxoside and the catalytic base Glu409, thus disrupting its function. Chemical modification of Asp375 has previously been shown to inactivate the enzyme. Taken together, the data suggest that Arg407, which belongs to the conserved sequence motif RPExxE, may act to modulate the activity of the enzyme. The proposed mechanism for modulating the activity is potentially a general mechanism for this superfamily.},
  author       = {Lobsanov, Yuri and Yoshida, Takashi and Desmet, Tom and Nerinckx, Wim and Yip, Patrick and Claeyssens, Marc and Herscovics, Annette and Howell, Lynne},
  issn         = {0907-4449},
  journal      = {ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY},
  keyword      = {ER-ASSOCIATED DEGRADATION,RETICULUM-ASSOCIATED DEGRADATION,MANNOSIDASE-LIKE PROTEIN,CLASS-I ALPHA-1,2-MANNOSIDASES,N-GLYCAN BIOSYNTHESIS,ENDOPLASMIC-RETICULUM,ALPHA-MANNOSIDASE,QUALITY-CONTROL,SACCHAROMYCES-CEREVISIAE,GLYCOPROTEIN-BIOSYNTHESIS},
  language     = {eng},
  number       = {3},
  pages        = {227--236},
  title        = {Modulation of activity by Arg407: structure of a fungal alpha-1,2-mannosidase in complex with a substrate analogue},
  url          = {http://dx.doi.org/10.1107/S0907444907065572},
  volume       = {64},
  year         = {2008},
}

Chicago
Lobsanov, Yuri, Takashi Yoshida, Tom Desmet, Wim Nerinckx, Patrick Yip, Marc Claeyssens, Annette Herscovics, and Lynne Howell. 2008. “Modulation of Activity by Arg407: Structure of a Fungal Alpha-1,2-mannosidase in Complex with a Substrate Analogue.” Acta Crystallographica Section D-biological Crystallography 64 (3): 227–236.
APA
Lobsanov, Y., Yoshida, T., Desmet, T., Nerinckx, W., Yip, P., Claeyssens, M., Herscovics, A., et al. (2008). Modulation of activity by Arg407: structure of a fungal alpha-1,2-mannosidase in complex with a substrate analogue. ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 64(3), 227–236.
Vancouver
1.
Lobsanov Y, Yoshida T, Desmet T, Nerinckx W, Yip P, Claeyssens M, et al. Modulation of activity by Arg407: structure of a fungal alpha-1,2-mannosidase in complex with a substrate analogue. ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY. 2008;64(3):227–36.
MLA
Lobsanov, Yuri, Takashi Yoshida, Tom Desmet, et al. “Modulation of Activity by Arg407: Structure of a Fungal Alpha-1,2-mannosidase in Complex with a Substrate Analogue.” ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY 64.3 (2008): 227–236. Print.