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PDBsum entry 1o7d

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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
1o7d
Jmol PyMol
Contents
Protein chains
292 a.a. *
76 a.a. *
151 a.a. *
270 a.a. *
109 a.a. *
Ligands
NAG ×6
TRS
SO4 ×2
NDG-NAG-BMA-MAN-
MAN-MAN-MAN-MAN-
MAN
NDG
Metals
_ZN
Waters ×39
* Residue conservation analysis
PDB id:
1o7d
Name: Hydrolase
Title: The structure of the bovine lysosomal a-mannosidase suggests a novel mechanism for low ph activation
Structure: Lysosomal alpha-mannosidase. Chain: a. Fragment: alpha-mannosidase a peptide, residues 51-347. Synonym: alpha-b mannosidase, lysosomal acid alpha- mannosidase, laman. Other_details: glycosylated. Lysosomal alpha-mannosidase. Chain: b. Fragment: alpha-mannosidase b peptide, residues 348-431.
Source: Bos taurus. Bovine. Organism_taxid: 9913. Organ: kidney. Organ: kidney
Biol. unit: Pentamer (from PDB file)
Resolution:
2.70Å     R-factor:   0.257     R-free:   0.289
Authors: P.Heikinheimo,R.Helland,H.S.Leiros,I.Leiros,S.Karlsen, G.Evjen,R.Ravelli,G.Schoehn,R.Ruigrok,O.-K.Tollersrud, S.Mcsweeney,E.Hough
Key ref:
P.Heikinheimo et al. (2003). The structure of bovine lysosomal alpha-mannosidase suggests a novel mechanism for low-pH activation. J Mol Biol, 327, 631-644. PubMed id: 12634058 DOI: 10.1016/S0022-2836(03)00172-4
Date:
30-Oct-02     Release date:   20-Mar-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q29451  (MA2B1_BOVIN) -  Lysosomal alpha-mannosidase
Seq:
Struc:
 
Seq:
Struc:
999 a.a.
292 a.a.
Protein chain
Pfam   ArchSchema ?
Q29451  (MA2B1_BOVIN) -  Lysosomal alpha-mannosidase
Seq:
Struc:
 
Seq:
Struc:
999 a.a.
76 a.a.
Protein chain
Pfam   ArchSchema ?
Q29451  (MA2B1_BOVIN) -  Lysosomal alpha-mannosidase
Seq:
Struc:
 
Seq:
Struc:
999 a.a.
151 a.a.
Protein chain
Pfam   ArchSchema ?
Q29451  (MA2B1_BOVIN) -  Lysosomal alpha-mannosidase
Seq:
Struc:
 
Seq:
Struc:
999 a.a.
270 a.a.
Protein chain
Pfam   ArchSchema ?
Q29451  (MA2B1_BOVIN) -  Lysosomal alpha-mannosidase
Seq:
Struc:
 
Seq:
Struc:
999 a.a.
109 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D, E: E.C.3.2.1.24  - Alpha-mannosidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     carbohydrate metabolic process   2 terms 
  Biochemical function     catalytic activity     6 terms  

 

 
DOI no: 10.1016/S0022-2836(03)00172-4 J Mol Biol 327:631-644 (2003)
PubMed id: 12634058  
 
 
The structure of bovine lysosomal alpha-mannosidase suggests a novel mechanism for low-pH activation.
P.Heikinheimo, R.Helland, H.K.Leiros, I.Leiros, S.Karlsen, G.Evjen, R.Ravelli, G.Schoehn, R.Ruigrok, O.K.Tollersrud, S.McSweeney, E.Hough.
 
  ABSTRACT  
 
Lysosomal alpha-mannosidase (LAM: EC 3.2.1.24) belongs to the sequence-based glycoside hydrolase family 38 (GH38). Two other mammalian GH38 members, Golgi alpha-mannosidase II (GIIAM) and cytosolic alpha-mannosidase, are expressed in all tissues. In humans, cattle, cat and guinea pig, lack of lysosomal alpha-mannosidase activity causes the autosomal recessive disease alpha-mannosidosis. Here, we describe the three-dimensional structure of bovine lysosomal alpha-mannosidase (bLAM) at 2.7A resolution and confirm the solution state dimer by electron microscopy. We present the first structure of a mammalian GH38 enzyme that offers indications for the signal areas for mannose phosphorylation, suggests a previously undetected mechanism of low-pH activation and provides a template for further biochemical studies of the family 38 glycoside hydrolases as well as lysosomal transport. Furthermore, it provides a basis for understanding the human form of alpha-mannosidosis at the atomic level. The atomic coordinates and structure factors have been deposited in the Protein Data Bank (accession codes 1o7d and r1o7dsf).
 
  Selected figure(s)  
 
Figure 7.
Figure 7. The charge surface on bLAM. The whole dimer is displayed, but charge surface is shown for only one monomer. Carbohydrate residues are in ball-and-stick format. The first GlcNAc residue at site D:N766 is indicated by an arrow and the label N766. Blue indicates positive charge, red indicates negative charge.
Figure 9.
Figure 9. A close-up of the hydrogen-bonding network on the C/D-peptide interface. Positively charged residues are blue, negative charged residues are red and neutral residues are yellow.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 327, 631-644) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21505070 E.Kuokkanen, H.M.Riise Stensland, W.Smith, E.Kjeldsen Buvang, L.Van Nguyen, O.Nilssen, and P.Heikinheimo (2011).
Molecular and cellular characterization of novel {alpha}-mannosidosis mutations.
  Hum Mol Genet, 20, 2651-2661.  
20209559 D.A.Kuntz, S.Nakayama, K.Shea, H.Hori, Y.Uto, H.Nagasawa, and D.R.Rose (2010).
Structural investigation of the binding of 5-substituted swainsonine analogues to Golgi alpha-mannosidase II.
  Chembiochem, 11, 673-680.
PDB codes: 3ejp 3ejq 3ejr 3ejs 3ejt 3eju
20798166 M.A.Hossain, R.Nakano, K.Nakamura, M.T.Hossain, and Y.Kimura (2010).
Molecular characterization of plant acidic alpha-mannosidase, a member of glycosylhydrolase family 38, involved in the turnover of N-glycans during tomato fruit ripening.
  J Biochem, 148, 603-616.  
20081828 Y.Zhu, M.D.Suits, A.J.Thompson, S.Chavan, Z.Dinev, C.Dumon, N.Smith, K.W.Moremen, Y.Xiang, A.Siriwardena, S.J.Williams, H.J.Gilbert, and G.J.Davies (2010).
Mechanistic insights into a Ca2+-dependent family of alpha-mannosidases in a human gut symbiont.
  Nat Chem Biol, 6, 125-132.
PDB codes: 2wvx 2wvy 2wvz 2ww0 2ww1 2ww2 2ww3 2wzs
19921429 Z.Roth, S.Parnes, S.Wiel, A.Sagi, N.Zmora, J.S.Chung, and I.Khalaila (2010).
N-glycan moieties of the crustacean egg yolk protein and their glycosylation sites.
  Glycoconj J, 27, 159-169.  
19722277 M.Venkatesan, D.A.Kuntz, and D.R.Rose (2009).
Human lysosomal alpha-mannosidases exhibit different inhibition and metal binding properties.
  Protein Sci, 18, 2242-2251.  
18651971 D.Malm, and ..Nilssen (2008).
Alpha-mannosidosis.
  Orphanet J Rare Dis, 3, 21.  
18599462 N.Shah, D.A.Kuntz, and D.R.Rose (2008).
Golgi alpha-mannosidase II cleaves two sugars sequentially in the same catalytic site.
  Proc Natl Acad Sci U S A, 105, 9570-9575.
PDB codes: 3cv5 3czn 3czs
17459873 M.Nagae, A.Tsuchiya, T.Katayama, K.Yamamoto, S.Wakatsuki, and R.Kato (2007).
Structural basis of the catalytic reaction mechanism of novel 1,2-alpha-L-fucosidase from Bifidobacterium bifidum.
  J Biol Chem, 282, 18497-18509.
PDB codes: 2eab 2eac 2ead 2eae
16510973 A.Dickmanns, M.Ballschmiter, W.Liebl, and R.Ficner (2006).
Structure of the novel alpha-amylase AmyC from Thermotoga maritima.
  Acta Crystallogr D Biol Crystallogr, 62, 262-270.
PDB code: 2b5d
16619322 I.Gitlin, J.D.Carbeck, and G.M.Whitesides (2006).
Why are proteins charged? Networks of charge-charge interactions in proteins measured by charge ladders and capillary electrophoresis.
  Angew Chem Int Ed Engl, 45, 3022-3060.  
16864579 K.Paschinger, M.Hackl, M.Gutternigg, D.Kretschmer-Lubich, U.Stemmer, V.Jantsch, G.Lochnit, and I.B.Wilson (2006).
A deletion in the golgi alpha-mannosidase II gene of Caenorhabditis elegans results in unexpected non-wild-type N-glycan structures.
  J Biol Chem, 281, 28265-28277.  
  16511275 M.Nakajima, S.Fushinobu, H.Imamura, H.Shoun, and T.Wakagi (2006).
Crystallization and preliminary X-ray analysis of cytosolic alpha-mannosidase from Thermotoga maritima.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 104-105.  
16115860 C.Park, L.Meng, L.H.Stanton, R.E.Collins, S.W.Mast, X.Yi, H.Strachan, and K.W.Moremen (2005).
Characterization of a human core-specific lysosomal {alpha}1,6-mannosidase involved in N-glycan catabolism.
  J Biol Chem, 280, 37204-37216.  
15663001 J.V.Lehtonen, D.J.Still, V.V.Rantanen, J.Ekholm, D.Björklund, Z.Iftikhar, M.Huhtala, S.Repo, A.Jussila, J.Jaakkola, O.Pentikäinen, T.Nyrönen, T.Salminen, M.Gyllenberg, and M.S.Johnson (2004).
BODIL: a molecular modeling environment for structure-function analysis and drug design.
  J Comput Aided Mol Des, 18, 401-419.  
15598351 S.Cheek, Y.Qi, S.S.Krishna, L.N.Kinch, and N.V.Grishin (2004).
4SCOPmap: automated assignment of protein structures to evolutionary superfamilies.
  BMC Bioinformatics, 5, 197.  
14636047 N.Shah, D.A.Kuntz, and D.R.Rose (2003).
Comparison of kifunensine and 1-deoxymannojirimycin binding to class I and II alpha-mannosidases demonstrates different saccharide distortions in inverting and retaining catalytic mechanisms.
  Biochemistry, 42, 13812-13816.
PDB code: 1ps3
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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