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PDBsum entry 1ktb

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Hydrolase PDB id
1ktb
Jmol
Contents
Protein chain
388 a.a. *
Ligands
NAG-NAG
NAG ×2
SO4 ×5
GOL ×12
ACY ×2
Waters ×401
* Residue conservation analysis
PDB id:
1ktb
Name: Hydrolase
Title: The structure of alpha-n-acetylgalactosaminidase
Structure: Alpha-n-acetylgalactosaminidase. Chain: a. Engineered: yes
Source: Gallus gallus. Chicken. Organism_taxid: 9031. Gene: alpha-naga. Expressed in: pichia pastoris. Expression_system_taxid: 4922.
Biol. unit: Dimer (from PDB file)
Resolution:
1.90Å     R-factor:   0.211     R-free:   0.222
Authors: S.C.Garman,L.Hannick,A.Zhu,D.N.Garboczi
Key ref:
S.C.Garman et al. (2002). The 1.9 A structure of alpha-N-acetylgalactosaminidase: molecular basis of glycosidase deficiency diseases. Structure, 10, 425-434. PubMed id: 12005440 DOI: 10.1016/S0969-2126(02)00726-8
Date:
15-Jan-02     Release date:   15-Mar-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q90744  (NAGAB_CHICK) -  Alpha-N-acetylgalactosaminidase
Seq:
Struc:
405 a.a.
388 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.3.2.1.49  - Alpha-N-acetylgalactosaminidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of terminal non-reducing N-acetyl-D-galactosamine residues in N-acetyl-alpha-D-galactosaminides.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     lysosome   1 term 
  Biological process     metabolic process   2 terms 
  Biochemical function     catalytic activity     5 terms  

 

 
DOI no: 10.1016/S0969-2126(02)00726-8 Structure 10:425-434 (2002)
PubMed id: 12005440  
 
 
The 1.9 A structure of alpha-N-acetylgalactosaminidase: molecular basis of glycosidase deficiency diseases.
S.C.Garman, L.Hannick, A.Zhu, D.N.Garboczi.
 
  ABSTRACT  
 
In the lysosome, glycosidases degrade glycolipids, glycoproteins, and oligosaccharides. Mutations in glycosidases cause disorders characterized by the deposition of undegraded carbohydrates. Schindler and Fabry diseases are caused by the incomplete degradation of carbohydrates with terminal alpha-N-acetylgalactosamine and alpha-galactose, respectively. Here we present the X-ray structure of alpha-N-acetylgalactosaminidase (alpha-NAGAL), the glycosidase that removes alpha-N-acetylgalactosamine, and the structure with bound ligand. The active site residues of alpha-NAGAL are conserved in the closely related enzyme a-galactosidase A (alpha-GAL). The structure demonstrates the catalytic mechanisms of both enzymes and reveals the structural basis of mutations causing Schindler and Fabry diseases. As alpha-NAGAL and alpha-GAL produce type O "universal donor" blood from type A and type B blood, the alpha-NAGAL structure will aid in the engineering of improved enzymes for blood conversion.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. The Active Site of a-NAGAL(A) The 1.9 electron density and active site residues from the native data set. A glycerol molecule appears in the active site, mimicking the location of the ligand.(B) The 2.4 electron density, a-GalNAc sugar, and active site residues from the protein complex with ligand, with residue numbers indicated. The orientation is identical to (A), and residues are colored as in Figure 2. The gray electron density maps (s[a]-weighted 2F[o] -F[c]-simulated annealing composite omit) are contoured at 1.6 s.(C) A cartoon diagram summarizing the interactions between the protein and a-GalNAc. The ligand is shown in bold, hydrogen bonds less than 3 in length are shown as red dashed lines, longer hydrogen bonds are shown as gray dashed lines, and van der Waals contacts are shown as blue dotted lines. Yellow boxes highlight residues that disrupt catalytic activity when mutated.
 
  The above figure is reprinted by permission from Cell Press: Structure (2002, 10, 425-434) copyright 2002.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20681989 H.Nakai, M.J.Baumann, B.O.Petersen, Y.Westphal, M.A.Hachem, A.Dilokpimol, J...Duus, H.A.Schols, and B.Svensson (2010).
Aspergillus nidulans alpha-galactosidase of glycoside hydrolase family 36 catalyses the formation of alpha-galacto-oligosaccharides by transglycosylation.
  FEBS J, 277, 3538-3551.  
19937437 T.Sakamoto, Y.Tsujitani, K.Fukamachi, Y.Taniguchi, and H.Ihara (2010).
Identification of two GH27 bifunctional proteins with beta-L-arabinopyranosidase/alpha-D-galactopyranosidase activities from Fusarium oxysporum.
  Appl Microbiol Biotechnol, 86, 1115-1124.  
18953653 A.Kumar, N.K.Singhal, B.Ramanujam, A.Mitra, N.R.Rameshwaram, S.K.Nadimpalli, and C.P.Rao (2009).
C(1)-/C(2)-aromatic-imino-glyco-conjugates: experimental and computational studies of binding, inhibition and docking aspects towards glycosidases isolated from soybean and jack bean.
  Glycoconj J, 26, 495-510.  
19683538 N.E.Clark, and S.C.Garman (2009).
The 1.9 a structure of human alpha-N-acetylgalactosaminidase: The molecular basis of Schindler and Kanzaki diseases.
  J Mol Biol, 393, 435-447.
PDB codes: 3h53 3h54 3h55 3igu
19853240 Y.Tajima, I.Kawashima, T.Tsukimura, K.Sugawara, M.Kuroda, T.Suzuki, T.Togawa, Y.Chiba, Y.Jigami, K.Ohno, T.Fukushige, T.Kanekura, K.Itoh, T.Ohashi, and H.Sakuraba (2009).
Use of a modified alpha-N-acetylgalactosaminidase in the development of enzyme replacement therapy for Fabry disease.
  Am J Hum Genet, 85, 569-580.  
19809163 Z.Fujimoto, S.Kaneko, W.D.Kim, G.G.Park, M.Momma, and H.Kobayashi (2009).
The tetramer structure of the glycoside hydrolase family 27 alpha-galactosidase I from Umbelopsis vinacea.
  Biosci Biotechnol Biochem, 73, 2360-2364.
PDB code: 3a5v
18443780 L.Weignerová, T.Filipi, D.Manglová, and V.Kren (2008).
Induction, purification and characterization of alpha-N-acetylgalactosaminidase from Aspergillus Niger.
  Appl Microbiol Biotechnol, 79, 769-774.  
18981178 M.Kitamura, M.Okuyama, F.Tanzawa, H.Mori, Y.Kitago, N.Watanabe, A.Kimura, I.Tanaka, and M.Yao (2008).
Structural and Functional Analysis of a Glycoside Hydrolase Family 97 Enzyme from Bacteroides thetaiotaomicron.
  J Biol Chem, 283, 36328-36337.
PDB codes: 2d73 2zq0
18214952 R.Minai, Y.Matsuo, H.Onuki, and H.Hirota (2008).
Method for comparing the structures of protein ligand-binding sites and application for predicting protein-drug interactions.
  Proteins, 72, 367-381.  
18848471 T.M.Gloster, J.P.Turkenburg, J.R.Potts, B.Henrissat, and G.J.Davies (2008).
Divergence of catalytic mechanism within a glycosidase family provides insight into evolution of carbohydrate metabolism by human gut flora.
  Chem Biol, 15, 1058-1067.
PDB codes: 2jka 2jke 2jkp
17206375 S.Li, T.Li, W.D.Kim, M.Kitaoka, S.Yoshida, M.Nakajima, and H.Kobayashi (2007).
Characterization of raffinose synthase from rice (Oryza sativa L. var. Nipponbare).
  Biotechnol Lett, 29, 635-640.  
  16511274 M.Foucault, H.Watzlawick, R.Mattes, R.Haser, and P.Gouet (2006).
Crystallization and preliminary X-ray diffraction studies of two thermostable alpha-galactosidases from glycoside hydrolase family 36.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 100-103.  
16547025 S.J.Brouns, N.Smits, H.Wu, A.P.Snijders, P.C.Wright, W.M.de Vos, and J.van der Oost (2006).
Identification of a novel alpha-galactosidase from the hyperthermophilic archaeon Sulfolobus solfataricus.
  J Bacteriol, 188, 2392-2399.  
16320365 S.W.Hinz, C.H.Doeswijk-Voragen, R.Schipperus, L.A.van den Broek, J.P.Vincken, and A.G.Voragen (2006).
Increasing the transglycosylation activity of alpha-galactosidase from Bifidobacterium adolescentis DSM 20083 by site-directed mutagenesis.
  Biotechnol Bioeng, 93, 122-131.  
16131397 D.G.Naumoff (2005).
GH97 is a new family of glycoside hydrolases, which is related to the alpha-galactosidase superfamily.
  BMC Genomics, 6, 112.  
15676072 J.Hujová, J.Sikora, R.Dobrovolný, H.Poupetová, J.Ledvinová, M.Kostrouchová, and M.Hrebícek (2005).
Characterization of gana-1, a Caenorhabditis elegans gene encoding a single ortholog of vertebrate alpha-galactosidase and alpha-N-acetylgalactosaminidase.
  BMC Cell Biol, 6, 5.  
14715651 G.Sulzenbacher, C.Bignon, T.Nishimura, C.A.Tarling, S.G.Withers, B.Henrissat, and Y.Bourne (2004).
Crystal structure of Thermotoga maritima alpha-L-fucosidase. Insights into the catalytic mechanism and the molecular basis for fucosidosis.
  J Biol Chem, 279, 13119-13128.
PDB codes: 1hl8 1hl9 1odu
14993697 M.Akita, M.Mizuno, T.Tonozuka, Y.Sakano, H.Matsui, Y.Hidaka, Y.Hatada, S.Ito, and K.Horikoshi (2004).
Crystallization and preliminary X-ray study of isomaltodextranase from Arthrobacter globiformis.
  Acta Crystallogr D Biol Crystallogr, 60, 572-573.  
15158631 O.A.Bodamer, R.Ratschmann, E.Paschke, T.Voigtländer, and S.Stöckler-Ipsiroglu (2004).
Recurrent acroparaesthesia during febrile infections.
  Lancet, 363, 1698.  
15604681 R.H.Lee, M.C.Lin, and S.C.Chen (2004).
A novel alkaline alpha-galactosidase gene is involved in rice leaf senescence.
  Plant Mol Biol, 55, 281-295.  
14635108 M.Yasuda, J.Shabbeer, S.D.Benson, I.Maire, R.M.Burnett, and R.J.Desnick (2003).
Fabry disease: characterization of alpha-galactosidase A double mutations and the D313Y plasma enzyme pseudodeficiency allele.
  Hum Mutat, 22, 486-492.  
12657636 Z.Fujimoto, S.Kaneko, M.Momma, H.Kobayashi, and H.Mizuno (2003).
Crystal structure of rice alpha-galactosidase complexed with D-galactose.
  J Biol Chem, 278, 20313-20318.
PDB code: 1uas
12413546 A.Vasella, G.J.Davies, and M.Böhm (2002).
Glycosidase mechanisms.
  Curr Opin Chem Biol, 6, 619-629.  
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.