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PDBsum entry 1vkj
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protein ligands Protein-protein interface(s) links
Transferase PDB id
1vkj

 

 

 

 

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Contents
Protein chains
258 a.a. *
Ligands
SO4 ×2
A3P ×3
Waters ×178
* Residue conservation analysis
PDB id:
1vkj
Name: Transferase
Title: Crystal structure of heparan sulfate 3-o-sulfotransferase isoform 1 in the presence of pap
Structure: Heparan sulfate (glucosamine) 3-o-sulfotransferase 1. Chain: a, b, c. Fragment: g48-h311. Engineered: yes. Mutation: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Trimer (from PQS)
Resolution:
2.50Å     R-factor:   0.243     R-free:   0.264
Authors: S.Thorp,K.A.Lee,M.Negishi,R.J.Linhardt,J.Liu,L.C.Pedersen
Key ref:
S.C.Edavettal et al. (2004). Crystal structure and mutational analysis of heparan sulfate 3-O-sulfotransferase isoform 1. J Biol Chem, 279, 25789-25797. PubMed id: 15060080 DOI: 10.1074/jbc.M401089200
Date:
25-May-04     Release date:   01-Jun-04    
Supersedes: 1s6t
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
O35310  (HS3S1_MOUSE) -  Heparan sulfate glucosamine 3-O-sulfotransferase 1 from Mus musculus
Seq:
Struc: 		311 a.a.
258 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.8.2.23  - [heparan sulfate]-glucosamine 3-sulfotransferase 1.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: alpha-D-glucosaminyl-[heparan sulfate](n) + 3'-phosphoadenylyl sulfate = 3-sulfo-alpha-D-glucosaminyl-[heparan sulfate](n) + adenosine 3',5'-bisphosphate + H+
alpha-D-glucosaminyl-[heparan sulfate](n)
 + 3'-phosphoadenylyl sulfate
 = 3-sulfo-alpha-D-glucosaminyl-[heparan sulfate](n)
 +
adenosine 3',5'-bisphosphate
Bound ligand (Het Group name = A3P)
corresponds exactly 		+ H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Added reference    
 
 
DOI no: 10.1074/jbc.M401089200 J Biol Chem 279:25789-25797 (2004)
PubMed id: 15060080  
 
 
Crystal structure and mutational analysis of heparan sulfate 3-O-sulfotransferase isoform 1.
S.C.Edavettal, K.A.Lee, M.Negishi, R.J.Linhardt, J.Liu, L.C.Pedersen.
 
  ABSTRACT  
 
Heparan sulfate interacts with antithrombin, a protease inhibitor, to regulate blood coagulation. Heparan sulfate 3-O-sulfotransferase isoform 1 performs the crucial last step modification in the biosynthesis of anticoagulant heparan sulfate. This enzyme transfers the sulfuryl group (SO(3)) from 3'-phosphoadenosine 5'-phosphosulfate to the 3-OH position of a glucosamine residue to form the 3-O-sulfo glucosamine, a structural motif critical for binding of heparan sulfate to antithrombin. In this study, we report the crystal structure of 3-O-sulfotransferase isoform 1 at 2.5-A resolution in a binary complex with 3'-phosphoadenosine 5'-phosphate. This structure reveals residues critical for 3'-phosphoadenosine 5'-phosphosulfate binding and suggests residues required for the binding of heparan sulfate. In addition, site-directed mutagenesis analyses suggest that residues Arg-67, Lys-68, Arg-72, Glu-90, His-92, Asp-95, Lys-123, and Arg-276 are essential for enzymatic activity. Among these essential amino acid residues, we find that residues Arg-67, Arg-72, His-92, and Asp-95 are conserved in heparan sulfate 3-O-sulfotransferases but not in heparan N-deacetylase/N-sulfotransferase, suggesting a role for these residues in conferring substrate specificity. Results from this study provide information essential for understanding the biosynthesis of anticoagulant heparan sulfate and the general mechanism of action of heparan sulfate sulfotransferases.
 
  Selected figure(s)  
 
Figure 1.
FIG. 1. The schematic biosynthesis of anticoagulant heparan sulfate. Five steps are involved in the biosynthesis of HS after the polysaccharide backbone is made. The numbers indicate the positions of each sugar unit. Both N-deacetylase/N-sulfotransferase and C[5]-epimerase modifications are indicated in red. The 2-O-sulfotransferase and 6-O-sulfotransferase modifications are indicated in black and blue, respectively. The 3-O-sulfotransferase modification is indicated in purple. For clarity, we have indicated the 3-O-sulfotransferase isoform 1 modifications only in this figure. GlcUA, glucuronic; IdoUA, iduronic acid; Glc, glucosamine. 		Figure 5.
FIG. 5. Charged surface diagram of the proposed heparan binding cleft of the sulfotransferase domains of NST-1 (a) and 3-OST-1 (b). The global position of the cleft is marked with a green dashed line. Blue surfaces signify positive charge, whereas red surfaces signify negative charge. The double-sided dash arrows (in green) indicate the region where HS may bind. This figure was created using Swiss PDB viewer.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 25789-25797) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20462768 L.M.Danan, Z.Yu, P.J.Ludden, W.Jia, K.L.Moore, and J.A.Leary (2010).
Catalytic mechanism of Golgi-resident human tyrosylprotein sulfotransferase-2: a mass spectrometry approach.
  J Am Soc Mass Spectrom, 21, 1633-1642.  
19591465 J.G.Martin, M.Gupta, Y.Xu, S.Akella, J.Liu, J.S.Dordick, and R.J.Linhardt (2009).
Toward an artificial Golgi: redesigning the biological activities of heparan sulfate on a digital microfluidic chip.
  J Am Chem Soc, 131, 11041-11048.  
19387498 S.Peterson, A.Frick, and J.Liu (2009).
Design of biologically active heparan sulfate and heparin using an enzyme-based approach.
  Nat Prod Rep, 26, 610-627.  
18928301 E.Tyapochkin, P.F.Cook, and G.Chen (2008).
Isotope exchange at equilibrium indicates a steady state ordered kinetic mechanism for human sulfotransferase.
  Biochemistry, 47, 11894-11899.  
19022906 H.N.Bethea, D.Xu, J.Liu, and L.C.Pedersen (2008).
Redirecting the substrate specificity of heparan sulfate 2-O-sulfotransferase by structurally guided mutagenesis.
  Proc Natl Acad Sci U S A, 105, 18724-18729.
PDB code: 3f5f
18625336 P.Bojarová, and S.J.Williams (2008).
Sulfotransferases, sulfatases and formylglycine-generating enzymes: a sulfation fascination.
  Curr Opin Chem Biol, 12, 573-581.  
17884631 J.Chen, C.L.Jones, and J.Liu (2007).
Using an enzymatic combinatorial approach to identify anticoagulant heparan sulfate structures.
  Chem Biol, 14, 986-993.  
17131147 J.Liu, and L.C.Pedersen (2007).
Anticoagulant heparan sulfate: structural specificity and biosynthesis.
  Appl Microbiol Biotechnol, 74, 263-272.  
16834555 R.Sasisekharan, R.Raman, and V.Prabhakar (2006).
Glycomics approach to structure-function relationships of glycosaminoglycans.
  Annu Rev Biomed Eng, 8, 181-231.  
15258569 J.D.Mougous, C.J.Petzold, R.H.Senaratne, D.H.Lee, D.L.Akey, F.L.Lin, S.E.Munchel, M.R.Pratt, L.W.Riley, J.A.Leary, J.M.Berger, and C.R.Bertozzi (2004).
Identification, function and structure of the mycobacterial sulfotransferase that initiates sulfolipid-1 biosynthesis.
  Nat Struct Mol Biol, 11, 721-729.
PDB code: 1tex
15574316 V.L.Rath, D.Verdugo, and S.Hemmerich (2004).
Sulfotransferase structural biology and inhibitor discovery.
  Drug Discov Today, 9, 1003-1011.  
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 code is shown on the right.

 

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