PDBsum entry 1kws

Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Transferase PDB id
Protein chain
250 a.a. *
UGA ×2
_MN ×2
Waters ×359
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of beta1,3-glucuronyltransferase i in complex with the active udp-glcua donor
Structure: Beta-1,3-glucuronyltransferase 3. Chain: a, b. Fragment: residue 76-335. Synonym: glucuronosyltransferase i. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
2.10Å     R-factor:   0.187     R-free:   0.223
Authors: L.C.Pedersen,T.A.Darden,M.Negishi
Key ref:
L.C.Pedersen et al. (2002). Crystal structure of beta 1,3-glucuronyltransferase I in complex with active donor substrate UDP-GlcUA. J Biol Chem, 277, 21869-21873. PubMed id: 11950836 DOI: 10.1074/jbc.M112343200
30-Jan-02     Release date:   19-Jun-02    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
O94766  (B3GA3_HUMAN) -  Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 3
335 a.a.
250 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Heparan and Chondroitin Biosynthesis
(early stages)
      Reaction: UDP-glucuronate + 3-beta-D-galactosyl-4-beta-D-galactosyl-O-beta-D- xylosylprotein = UDP + 3-beta-D-glucuronosyl-3-beta-D-galactosyl-4-beta- D-galactosyl-O-beta-D-xylosylprotein
Bound ligand (Het Group name = UGA)
corresponds exactly
+ 3-beta-D-galactosyl-4-beta-D-galactosyl-O-beta-D- xylosylprotein
+ 3-beta-D-glucuronosyl-3-beta-D-galactosyl-4-beta- D-galactosyl-O-beta-D-xylosylprotein
      Cofactor: Mn(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biochemical function     galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase activity     1 term  


DOI no: 10.1074/jbc.M112343200 J Biol Chem 277:21869-21873 (2002)
PubMed id: 11950836  
Crystal structure of beta 1,3-glucuronyltransferase I in complex with active donor substrate UDP-GlcUA.
L.C.Pedersen, T.A.Darden, M.Negishi.
Beta1,3-glucuronyltransferase (GlcAT-I) is an essential enzyme involved in heparan sulfate and chondroitin sulfate biosynthesis. GlcAT-I is an inverting glycosyltransferase that catalyzes the transfer of glucuronic acid (GlcUA) to the common growing linker region Galbeta1-3Galbeta1-4Xyl that is attached to a serine side chain of a core protein. Previously the structure of GlcAT-I has been solved in the presence of the donor product UDP and an acceptor analog Galbeta1-3Galbeta1-4Xyl (Pedersen, L. C., Tsuchida, K., Kitagawa, H., Sugahara, K., Darden, T. A. & Negishi, M. (2000) J. Biol. Chem. 275, 34580-34585). Here we report the x-ray crystal structure of GlcAT-I in complex with the complete donor UDP-GlcUA, thereby providing structures of an inverting glycosyltransferase in which both the complete donor and acceptor substrates are present in the active site. This structure supports the in-line displacement reaction mechanism previously proposed. It also provides information on the essential amino acid residues that determine donor substrate specificity.
  Selected figure(s)  
Figure 1.
Fig. 1. Left, stereo diagram of the UDP-GlcUA donor binding site in GlcAT-I. Residues involved in binding UDP-GlcUA are displayed in khaki with the UDP-GlcUA molecule displayed in yellow. Hydrogen bonds are represented as black dashed lines whereas dark green dashed lines represent interactions between the manganese atom and atoms coordinated to it. An F[o] F[c] annealed omit map of the UDP-GlcUA is shown in light blue contoured at 5 (figure created using Molscript (27) and Raster3D (28)). Right, chemical structure of UDP-GlcUA.
Figure 4.
Fig. 4. Stereo superposition of the crystal structure of LgtC with bound donor UDP 2-deoxy-2-fluorogalactose and acceptor 4'-deoxylactose substrate analogs (cornflower blue) to the structures of GlcAT-I with bound UDP-GlcUA and Gal 1-3Gal (dark orange). Residues found in similar positions in the two structures are shown. This superposition is based on the position of the C-5 of the ribose, the and phosphates, and the C-1 carbon of the donor sugar of the UDP-sugar donor substrates (figure created using Molscript (27) and Raster3D (28)).
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 21869-21873) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20655926 B.Schuman, M.Persson, R.C.Landry, R.Polakowski, J.T.Weadge, N.O.Seto, S.N.Borisova, M.M.Palcic, and S.V.Evans (2010).
Cysteine-to-serine mutants dramatically reorder the active site of human ABO(H) blood group B glycosyltransferase without affecting activity: structural insights into cooperative substrate binding.
  J Mol Biol, 402, 399-411.
PDB codes: 3i0c 3i0d 3i0e 3i0f 3i0g 3i0h 3i0i 3i0j 3i0k 3i0l
20672277 G.K.Wagner, and T.Pesnot (2010).
Glycosyltransferases and their assays.
  Chembiochem, 11, 1939-1949.  
  20585355 L.Kaminski, and J.Eichler (2010).
Identification of residues important for the activity of Haloferax volcanii AglD, a component of the archaeal N-glycosylation pathway.
  Archaea, 2010, 315108.  
  19058170 C.J.Thibodeaux, C.E.Melançon, and H.W.Liu (2008).
Natural-product sugar biosynthesis and enzymatic glycodiversification.
  Angew Chem Int Ed Engl, 47, 9814-9859.  
18627619 C.J.Zea, G.Camci-Unal, and N.L.Pohl (2008).
Thermodynamics of binding of divalent magnesium and manganese to uridine phosphates: implications for diabetes-related hypomagnesaemia and carbohydrate biocatalysis.
  Chem Cent J, 2, 15.  
18518825 L.L.Lairson, B.Henrissat, G.J.Davies, and S.G.Withers (2008).
Glycosyltransferases: structures, functions, and mechanisms.
  Annu Rev Biochem, 77, 521-555.  
17460661 C.J.Thibodeaux, C.E.Melançon, and H.W.Liu (2007).
Unusual sugar biosynthesis and natural product glycodiversification.
  Nature, 446, 1008-1016.  
16840342 E.T.Larson, D.Reiter, M.Young, and C.M.Lawrence (2006).
Structure of A197 from Sulfolobus turreted icosahedral virus: a crenarchaeal viral glycosyltransferase exhibiting the GT-A fold.
  J Virol, 80, 7636-7644.
PDB code: 2c0n
16815917 M.Fondeur-Gelinotte, V.Lattard, R.Oriol, R.Mollicone, J.C.Jacquinet, G.Mulliert, S.Gulberti, P.Netter, J.Magdalou, M.Ouzzine, and S.Fournel-Gigleux (2006).
Phylogenetic and mutational analyses reveal key residues for UDP-glucuronic acid binding and activity of beta1,3-glucuronosyltransferase I (GlcAT-I).
  Protein Sci, 15, 1667-1678.  
16584127 P.K.Qasba, B.Ramakrishnan, and E.Boeggeman (2006).
Mutant glycosyltransferases assist in the development of a targeted drug delivery system and contrast agents for MRI.
  AAPS J, 8, E190-E195.  
16897771 T.Shiba, S.Kakuda, M.Ishiguro, I.Morita, S.Oka, T.Kawasaki, S.Wakatsuki, and R.Kato (2006).
Crystal structure of GlcAT-S, a human glucuronyltransferase, involved in the biosynthesis of the HNK-1 carbohydrate epitope.
  Proteins, 65, 499-508.
PDB code: 2d0j
16007668 C.J.Zea, and N.L.Pohl (2005).
Unusual sugar nucleotide recognition elements of mesophilic vs. thermophilic glycogen synthases.
  Biopolymers, 79, 106-113.  
15653326 P.K.Qasba, B.Ramakrishnan, and E.Boeggeman (2005).
Substrate-induced conformational changes in glycosyltransferases.
  Trends Biochem Sci, 30, 53-62.  
12743367 T.Correia, V.Papayannopoulos, V.Panin, P.Woronoff, J.Jiang, T.F.Vogt, and K.D.Irvine (2003).
Molecular genetic analysis of the glycosyltransferase Fringe in Drosophila.
  Proc Natl Acad Sci U S A, 100, 6404-6409.  
12538870 Y.Hu, L.Chen, S.Ha, B.Gross, B.Falcone, D.Walker, M.Mokhtarzadeh, and S.Walker (2003).
Crystal structure of the MurG:UDP-GlcNAc complex reveals common structural principles of a superfamily of glycosyltransferases.
  Proc Natl Acad Sci U S A, 100, 845-849.
PDB code: 1nlm
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.