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PDBsum entry 1bhg

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Glycosidase PDB id
1bhg
Jmol
Contents
Protein chain
611 a.a. *
Ligands
NAG-NAG-BMA-MAN-
MAN-MAN-MAN-MAN-
MAN
×2
* Residue conservation analysis
PDB id:
1bhg
Name: Glycosidase
Title: Human beta-glucuronidase at 2.6 a resolution
Structure: Beta-glucuronidase. Chain: a, b. Synonym: gus gene product. Engineered: yes. Other_details: lysosomal enzyme
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: mouse l-cell line. Organ: placenta. Organelle: lysosome. Gene: human placental gus gene cdna. Expressed in: mus musculus. Expression_system_taxid: 10090.
Biol. unit: Homo-Tetramer (from PDB file)
Resolution:
2.53Å     R-factor:   0.231     R-free:   0.310
Authors: S.Jain,W.B.Drendel
Key ref: S.Jain et al. (1996). Structure of human beta-glucuronidase reveals candidate lysosomal targeting and active-site motifs. Nat Struct Biol, 3, 375-381. PubMed id: 8599764
Date:
04-Mar-96     Release date:   17-Sep-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P08236  (BGLR_HUMAN) -  Beta-glucuronidase
Seq:
Struc:
 
Seq:
Struc:
651 a.a.
611 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.2.1.31  - Beta-glucuronidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: A beta-D-glucuronoside + H2O = D-glucuronate + an alcohol
beta-D-glucuronoside
+ H(2)O
=
D-glucuronate
Bound ligand (Het Group name = BMA)
matches with 84.62% similarity
+ alcohol
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     carbohydrate metabolic process   1 term 
  Biochemical function     hydrolase activity, hydrolyzing O-glycosyl compounds     1 term  

 

 
    reference    
 
 
Nat Struct Biol 3:375-381 (1996)
PubMed id: 8599764  
 
 
Structure of human beta-glucuronidase reveals candidate lysosomal targeting and active-site motifs.
S.Jain, W.B.Drendel, Z.W.Chen, F.S.Mathews, W.S.Sly, J.H.Grubb.
 
  ABSTRACT  
 
The X-ray structure of the homotetrameric lysosomal acid hydrolase, human beta-glucuronidase (332,000 Mr), has been determined at 2.6 A resolution. The tetramer has approximate dihedral symmetry and each promoter consists of three structural domains with topologies similar to a jelly roll barrel, an immunoglobulin constant domain and a TIM barrel respectively. Residues 179-204 form a beta-hairpin motif similar to the putative lysosomal targeting motif of cathepsin D, supporting the view that lysosomal targeting has a structural basis. The active site of the enzyme is formed from a large cleft at the interface of two monomers. Residues Glu 451 and Glu 540 are proposed to be important for catalysis. The structure establishes a framework for understanding mutations that lead to the human genetic disease mucopolysaccharidosis VII, and for using the enzyme in anti-cancer therapy.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21465555 M.Sikora, and M.Cieplak (2011).
Mechanical stability of multidomain proteins and novel mechanical clamps.
  Proteins, 79, 1786-1799.  
21051639 B.D.Wallace, H.Wang, K.T.Lane, J.E.Scott, J.Orans, J.S.Koo, M.Venkatesh, C.Jobin, L.A.Yeh, S.Mani, and M.R.Redinbo (2010).
Alleviating cancer drug toxicity by inhibiting a bacterial enzyme.
  Science, 330, 831-835.
PDB codes: 3k46 3k4a 3k4d 3lpf 3lpg
20601499 S.Potot, C.R.Serra, A.O.Henriques, and G.Schyns (2010).
Display of recombinant proteins on Bacillus subtilis spores, using a coat-associated enzyme as the carrier.
  Appl Environ Microbiol, 76, 5926-5933.  
19097997 R.Hurtado-Guerrero, A.W.Schüttelkopf, I.Mouyna, A.F.Ibrahim, S.Shepherd, T.Fontaine, J.P.Latgé, and D.M.van Aalten (2009).
Molecular mechanisms of yeast cell wall glucan remodeling.
  J Biol Chem, 284, 8461-8469.
PDB codes: 2w61 2w62 2w63
19224584 S.Tomatsu, A.M.Montaño, V.C.Dung, J.H.Grubb, and W.S.Sly (2009).
Mutations and polymorphisms in GUSB gene in mucopolysaccharidosis VII (Sly Syndrome).
  Hum Mutat, 30, 511-519.  
19171971 T.Lütteke (2009).
Analysis and validation of carbohydrate three-dimensional structures.
  Acta Crystallogr D Biol Crystallogr, 65, 156-168.  
19101472 K.C.Chen, C.H.Wu, C.Y.Chang, W.C.Lu, Q.Tseng, Z.M.Prijovich, W.Schechinger, Y.C.Liaw, Y.L.Leu, and S.R.Roffler (2008).
Directed evolution of a lysosomal enzyme with enhanced activity at neutral pH by mammalian cell-surface display.
  Chem Biol, 15, 1277-1286.  
  19255633 L.Arul, G.Benita, D.Sudhakar, B.Thayumanavan, and P.Balasubramanian (2008).
beta-glucuronidase of family-2 glycosyl hydrolase: A missing member in plants.
  Bioinformation, 3, 194-197.  
  18685721 L.Arul, G.Benita, and P.Balasubramanian (2008).
Functional insight for beta-glucuronidase in Escherichia coli and Staphylococcus sp. RLH1.
  Bioinformation, 2, 339-343.  
17140411 D.G.Longstaff, S.K.Blight, L.Zhang, K.B.Green-Church, and J.A.Krzycki (2007).
In vivo contextual requirements for UAG translation as pyrrolysine.
  Mol Microbiol, 63, 229-241.  
16977328 K.C.Chen, T.L.Cheng, Y.L.Leu, Z.M.Prijovich, C.H.Chuang, B.M.Chen, and S.R.Roffler (2007).
Membrane-localized activation of glucuronide prodrugs by beta-glucuronidase enzymes.
  Cancer Gene Ther, 14, 187-200.  
17287210 L.E.Tailford, V.A.Money, N.L.Smith, C.Dumon, G.J.Davies, and H.J.Gilbert (2007).
Mannose foraging by Bacteroides thetaiotaomicron: structure and specificity of the beta-mannosidase, BtMan2A.
  J Biol Chem, 282, 11291-11299.
PDB code: 2je8
17467736 M.L.Geddie, and I.Matsumura (2007).
Antibody-induced oligomerization and activation of an engineered reporter enzyme.
  J Mol Biol, 369, 1052-1059.  
16636831 M.Ike, K.Isami, Y.Tanabe, M.Nogawa, W.Ogasawara, H.Okada, and Y.Morikawa (2006).
Cloning and heterologous expression of the exo-beta-D-glucosaminidase-encoding gene (gls93) from a filamentous fungus, Trichoderma reesei PC-3-7.
  Appl Microbiol Biotechnol, 72, 687-695.  
16272959 M.Gratz, C.Kunert-Keil, U.John, I.Cascorbi, and H.K.Kroemer (2005).
Identification and functional analysis of genetic variants of the human beta-glucuronidase in a German population sample.
  Pharmacogenet Genomics, 15, 875-881.  
15526106 C.Kunert-Keil, B.Sperker, S.Bien, G.Wolf, M.Grube, and H.K.Kroemer (2004).
Involvement of AP-2 binding sites in regulation of human beta-glucuronidase.
  Naunyn Schmiedebergs Arch Pharmacol, 370, 331-339.  
15069062 M.L.Geddie, and I.Matsumura (2004).
Rapid evolution of beta-glucuronidase specificity by saturation mutagenesis of an active site loop.
  J Biol Chem, 279, 26462-26468.  
12783870 A.Yaghootfam, F.Schestag, T.Dierks, and V.Gieselmann (2003).
Recognition of arylsulfatase A and B by the UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-phosphotransferase.
  J Biol Chem, 278, 32653-32661.  
12700165 S.Tomatsu, K.O.Orii, C.Vogler, J.H.Grubb, E.M.Snella, M.Gutierrez, T.Dieter, C.C.Holden, K.Sukegawa, T.Orii, N.Kondo, and W.S.Sly (2003).
Production of MPS VII mouse (Gus(tm(hE540A x mE536A)Sly)) doubly tolerant to human and mouse beta-glucuronidase.
  Hum Mol Genet, 12, 961-973.  
11799115 M.K.Hancock, D.J.Haskins, G.Sun, and N.M.Dahms (2002).
Identification of residues essential for carbohydrate recognition by the insulin-like growth factor II/mannose 6-phosphate receptor.
  J Biol Chem, 277, 11255-11264.  
12374794 M.K.Hancock, R.D.Yammani, and N.M.Dahms (2002).
Localization of the carbohydrate recognition sites of the insulin-like growth factor II/mannose 6-phosphate receptor to domains 3 and 9 of the extracytoplasmic region.
  J Biol Chem, 277, 47205-47212.  
12403825 S.Tomatsu, K.O.Orii, C.Vogler, J.H.Grubb, E.M.Snella, M.A.Gutierrez, T.Dieter, K.Sukegawa, T.Orii, N.Kondo, and W.S.Sly (2002).
Missense models [Gustm(E536A)Sly, Gustm(E536Q)Sly, and Gustm(L175F)Sly] of murine mucopolysaccharidosis type VII produced by targeted mutagenesis.
  Proc Natl Acad Sci U S A, 99, 14982-14987.  
11358516 P.Ademark, R.P.de Vries, P.Hägglund, H.Stålbrand, and J.Visser (2001).
Cloning and characterization of Aspergillus niger genes encoding an alpha-galactosidase and a beta-mannosidase involved in galactomannan degradation.
  Eur J Biochem, 268, 2982-2990.  
10694390 P.G.Marron-Terada, M.K.Hancock, D.J.Haskins, and N.M.Dahms (2000).
Recognition of Dictyostelium discoideum lysosomal enzymes is conferred by the amino-terminal carbohydrate binding site of the insulin-like growth factor II/mannose 6-phosphate receptor.
  Biochemistry, 39, 2243-2253.  
11080624 Z.Marković-Housley, G.Miglierini, L.Soldatova, P.J.Rizkallah, U.Müller, and T.Schirmer (2000).
Crystal structure of hyaluronidase, a major allergen of bee venom.
  Structure, 8, 1025-1035.
PDB codes: 1fcq 1fcu 1fcv
9920914 A.Schierau, F.Dietz, H.Lange, F.Schestag, A.Parastar, and V.Gieselmann (1999).
Interaction of arylsulfatase A with UDP-N-acetylglucosamine:Lysosomal enzyme-N-acetylglucosamine-1-phosphotransferase.
  J Biol Chem, 274, 3651-3658.  
  10210191 D.H.Juers, R.E.Huber, and B.W.Matthews (1999).
Structural comparisons of TIM barrel proteins suggest functional and evolutionary relationships between beta-galactosidase and other glycohydrolases.
  Protein Sci, 8, 122-136.  
10438523 M.R.Islam, S.Tomatsu, G.N.Shah, J.H.Grubb, S.Jain, and W.S.Sly (1999).
Active site residues of human beta-glucuronidase. Evidence for Glu(540) as the nucleophile and Glu(451) as the acid-base residue.
  J Biol Chem, 274, 23451-23455.  
9852062 A.W.Wong, S.He, J.H.Grubb, W.S.Sly, and S.G.Withers (1998).
Identification of Glu-540 as the catalytic nucleophile of human beta-glucuronidase using electrospray mass spectrometry.
  J Biol Chem, 273, 34057-34062.  
9604938 D.L.Roberts, D.J.Weix, N.M.Dahms, and J.J.Kim (1998).
Molecular basis of lysosomal enzyme recognition: three-dimensional structure of the cation-dependent mannose 6-phosphate receptor.
  Cell, 93, 639-648.
PDB code: 1m6p
9525982 L.H.O'Connor, L.C.Erway, C.A.Vogler, W.S.Sly, A.Nicholes, J.Grubb, S.W.Holmberg, B.Levy, and M.S.Sands (1998).
Enzyme replacement therapy for murine mucopolysaccharidosis type VII leads to improvements in behavior and auditory function.
  J Clin Invest, 101, 1394-1400.  
9345621 B.Henrissat, and G.Davies (1997).
Structural and sequence-based classification of glycoside hydrolases.
  Curr Opin Struct Biol, 7, 637-644.  
9032078 C.S.Bond, P.R.Clements, S.J.Ashby, C.A.Collyer, S.J.Harrop, J.J.Hopwood, and J.M.Guss (1997).
Structure of a human lysosomal sulfatase.
  Structure, 5, 277-289.
PDB code: 1fsu
9362483 R.Tikkanen, M.Peltola, C.Oinonen, J.Rouvinen, and L.Peltonen (1997).
Several cooperating binding sites mediate the interaction of a lysosomal enzyme with phosphotransferase.
  EMBO J, 16, 6684-6693.  
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.