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PDBsum entry 1q20

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protein ligands metals links
Transferase PDB id
1q20
Jmol
Contents
Protein chain
294 a.a. *
Ligands
A3P
PLO
Metals
_NA
Waters ×118
* Residue conservation analysis
PDB id:
1q20
Name: Transferase
Title: Crystal structure of human cholesterol sulfotransferase (sult2b1b) in the presence of pap and pregnenolone
Structure: Sulfotransferase family, cytosolic, 2b, member 1 isoform b. Chain: a. Synonym: sult2b1b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: sult2b1. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.30Å     R-factor:   0.211     R-free:   0.225
Authors: K.A.Lee,H.Fuda,Y.C.Lee,M.Negishi,C.A.Strott,L.C.Pedersen
Key ref:
K.A.Lee et al. (2003). Crystal structure of human cholesterol sulfotransferase (SULT2B1b) in the presence of pregnenolone and 3'-phosphoadenosine 5'-phosphate. Rationale for specificity differences between prototypical SULT2A1 and the SULT2BG1 isoforms. J Biol Chem, 278, 44593-44599. PubMed id: 12923182 DOI: 10.1074/jbc.M308312200
Date:
23-Jul-03     Release date:   11-Nov-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O00204  (ST2B1_HUMAN) -  Sulfotransferase family cytosolic 2B member 1
Seq:
Struc:
365 a.a.
294 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.2.8.2.2  - Alcohol sulfotransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 3'-phosphoadenylyl sulfate + an alcohol = adenosine 3',5'-bisphosphate + an alkyl sulfate
3'-phosphoadenylyl sulfate
+ alcohol
=
adenosine 3',5'-bisphosphate
Bound ligand (Het Group name = A3P)
corresponds exactly
+ alkyl sulfate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     sulfotransferase activity     1 term  

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M308312200 J Biol Chem 278:44593-44599 (2003)
PubMed id: 12923182  
 
 
Crystal structure of human cholesterol sulfotransferase (SULT2B1b) in the presence of pregnenolone and 3'-phosphoadenosine 5'-phosphate. Rationale for specificity differences between prototypical SULT2A1 and the SULT2BG1 isoforms.
K.A.Lee, H.Fuda, Y.C.Lee, M.Negishi, C.A.Strott, L.C.Pedersen.
 
  ABSTRACT  
 
The gene for human hydroxysteroid sulfotransferase (SULT2B1) encodes two peptides, SULT2B1a and SULT2B1b, that differ only at their amino termini. SULT2B1b has a predilection for cholesterol but is also capable of sulfonating pregnenolone, whereas SULT2B1a preferentially sulfonates pregnenolone and only minimally sulfonates cholesterol. We have determined the crystal structure of SULT2B1a and SULT2B1b bound to the substrate donor product 3'-phosphoadenosine 5'-phosphate at 2.9 and 2.4 A, respectively, as well as SULT2B1b in the presence of the acceptor substrate pregnenolone at 2.3 A. These structures reveal a different catalytic binding orientation for the substrate from a previously determined structure of hydroxysteroid sulfotransferase (SULT2A1) binding dehydroepiandrosterone. In addition, the amino-terminal helix comprising residues Asp19 to Lys26, which determines the specificity difference between the SULT2B1 isoforms, becomes ordered upon pregnenolone binding, covering the substrate binding pocket.
 
  Selected figure(s)  
 
Figure 2.
FIG. 2. a, stereodiagram of the PAPS binding site of SULT2B1b with PAP (orange) bound. Hydrogen bonds are shown by dashed black lines. b, superposition of the active sites of human EST with PAPS bound (green) and SULT2B1 (khaki) with PAP (orange) and pregnenolone (light blue) bound (based on superposition of PSB-loops). The catalytic Ser155, Lys70, and His125 are shown pictured with hydrogen bonds (black dashed lines) to the bridging oxygen of PAP and the acceptor O3 oxygen of pregnenolone. Hydrogen bonds between human EST and PAPS are shown as pink dashed lines. The sulfur atom from PAPS is shown in yellow.A dashed orange line has been drawn from the acceptor O3 oxygen of the pregnenolone molecule to the leaving group bridging oxygen of PAP. This line goes right through the sulfur supporting the proposed S[N]2-like in-line displacement mechanism. This figure was created using MOLSCRIPT and Raster3D (31, 32).
Figure 4.
FIG. 4. Superposition of acceptor substrates from human EST and SULT2A1 onto the active site of SULT2B1 with pregnenolone bound (17 -estradiol (green) from the crystal structure of human EST (24), alternate binding conformations of DHEA to SULT2A1, catalytic (purple), and substrate inhibition site (yellow)). Superpositions are based on all of the structurally equivalent C atoms. Residues from the SULT2B1b (khaki) that are likely to form steric clashes if pregnenolone bound in the same catalytic binding orientation as 17 -estradiol to human EST or DHEA to SULT2A1 are shown. This figure was created using MOLSCRIPT and Raster3D (31, 32).
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 44593-44599) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20718863 K.Kurogi, Y.Sakakibara, Y.Kamemoto, S.Takahashi, S.Yasuda, M.C.Liu, and M.Suiko (2010).
Mouse cytosolic sulfotransferase SULT2B1b interacts with cytoskeletal proteins via a proline/serine-rich C-terminus.
  FEBS J, 277, 3804-3811.  
18831774 A.K.Dunker, C.J.Oldfield, J.Meng, P.Romero, J.Y.Yang, J.W.Chen, V.Vacic, Z.Obradovic, and V.N.Uversky (2008).
The unfoldomics decade: an update on intrinsically disordered proteins.
  BMC Genomics, 9, S1.  
18366598 C.J.Oldfield, J.Meng, J.Y.Yang, M.Q.Yang, V.N.Uversky, and A.K.Dunker (2008).
Flexible nets: disorder and induced fit in the associations of p53 and 14-3-3 with their partners.
  BMC Genomics, 9, S1.  
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.  
17425406 A.Allali-Hassani, P.W.Pan, L.Dombrovski, R.Najmanovich, W.Tempel, A.Dong, P.Loppnau, F.Martin, J.Thornton, J.Thonton, A.M.Edwards, A.Bochkarev, A.N.Plotnikov, M.Vedadi, and C.H.Arrowsmith (2007).
Structural and chemical profiling of the human cytosolic sulfotransferases.
  PLoS Biol, 5, e97.
PDB codes: 1zd1 2ad1 2gwh 2h8k
16801938 M.A.Hildebrandt, D.P.Carrington, B.A.Thomae, B.W.Eckloff, D.J.Schaid, V.C.Yee, R.M.Weinshilboum, and E.D.Wieben (2007).
Genetic diversity and function in the human cytosolic sulfotransferases.
  Pharmacogenomics J, 7, 133-143.  
17055258 C.N.Falany, D.He, N.Dumas, A.R.Frost, and J.L.Falany (2006).
Human cytosolic sulfotransferase 2B1: isoform expression, tissue specificity and subcellular localization.
  J Steroid Biochem Mol Biol, 102, 214-221.  
16717195 P.R.Romero, S.Zaidi, Y.Y.Fang, V.N.Uversky, P.Radivojac, C.J.Oldfield, M.S.Cortese, M.Sickmeier, T.LeGall, Z.Obradovic, and A.K.Dunker (2006).
Alternative splicing in concert with protein intrinsic disorder enables increased functional diversity in multicellular organisms.
  Proc Natl Acad Sci U S A, 103, 8390-8395.  
15608121 S.Pakhomova, J.Buck, and M.E.Newcomer (2005).
The structures of the unique sulfotransferase retinol dehydratase with product and inhibitors provide insight into enzyme mechanism and inhibition.
  Protein Sci, 14, 176-182.
PDB codes: 1x8j 1x8k 1x8l
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 codes are shown on the right.