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PDBsum entry 2d06

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protein ligands Protein-protein interface(s) links
Transferase PDB id
2d06
Jmol
Contents
Protein chain
288 a.a. *
Ligands
A3P ×2
EST ×2
Waters ×119
* Residue conservation analysis
PDB id:
2d06
Name: Transferase
Title: Human sult1a1 complexed with pap and estradiol
Structure: Sulfotransferase 1a1. Chain: a, b. Synonym: sult1a1, phenol sulfotransferase 1, aryl sulfotransferase 1, phenol-sulfating phenol sulfotransferase 1, p- pst 1, thermostable phenol sulfotransferase, ts-pst, hast1/hast2, st1a3. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: liver. Gene: sult1a1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
2.30Å     R-factor:   0.217     R-free:   0.283
Authors: N.U.Gamage,S.Tsvetanov,R.G.Duggleby,M.E.Mcmanus,J.L.Martin
Key ref:
N.U.Gamage et al. (2005). The structure of human SULT1A1 crystallized with estradiol. An insight into active site plasticity and substrate inhibition with multi-ring substrates. J Biol Chem, 280, 41482-41486. PubMed id: 16221673 DOI: 10.1074/jbc.M508289200
Date:
25-Jul-05     Release date:   25-Oct-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P50225  (ST1A1_HUMAN) -  Sulfotransferase 1A1
Seq:
Struc:
295 a.a.
288 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.2.8.2.1  - Aryl sulfotransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 3'-phosphoadenylyl sulfate + a phenol = adenosine 3',5'-bisphosphate + an aryl sulfate
3'-phosphoadenylyl sulfate
+ phenol
=
adenosine 3',5'-bisphosphate
Bound ligand (Het Group name = A3P)
corresponds exactly
+ aryl sulfate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   2 terms 
  Biological process     small molecule metabolic process   10 terms 
  Biochemical function     transferase activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M508289200 J Biol Chem 280:41482-41486 (2005)
PubMed id: 16221673  
 
 
The structure of human SULT1A1 crystallized with estradiol. An insight into active site plasticity and substrate inhibition with multi-ring substrates.
N.U.Gamage, S.Tsvetanov, R.G.Duggleby, M.E.McManus, J.L.Martin.
 
  ABSTRACT  
 
Human SULT1A1 belongs to the supergene family of sulfotransferases (SULTs) involved in the sulfonation of xeno- and endobiotics. The enzyme is also one of the SULTs responsible for metabolic activation of mutagenic and carcinogenic compounds and therefore is implicated in various cancer forms. Further, it is not well understood how substrate inhibition takes place with rigid fused multiring substrates such as 17beta-estradiol (E2) at high substrate concentrations when subcellular fractions or recombinant enzymes are used. To investigate how estradiol binds to SULT1A1, we co-crystallized SULT1A1 with sulfated estradiol and the cofactor product, PAP (3'-phosphoadenosine 5'-phosphate). The crystal structure of SULT1A1 that we present here has PAP and one molecule of E2 bound in a nonproductive mode in the active site. The structure reveals how the SULT1A1 binding site undergoes conformational changes to accept fused ring substrates such as steroids. In agreement with previous reports, the enzyme shows partial substrate inhibition at high concentrations of E2. A model to explain these kinetics is developed based on the formation of an enzyme x PAP x E2 dead-end complex during catalysis. This model provides a very curve. This dead-end complex is proposed to be that described by the observed structure, where E2 is bound in a nonproductive mode.
 
  Selected figure(s)  
 
Figure 2.
FIGURE 2. Comparison of fused ring substrate binding in SULT1A1, mouse SULT1E1, and human SULT2A1. A, stereoview of E2 binding in the SULT1A1 active site. The noncatalytic substrate binding mode of SULT1A1 is shown in orange. The O-3 hydroxyl of E2 can form hydrogen bonds (dotted lines) to PAP and Lys48 (not shown for clarity). The proposed E2 catalytic orientation (green) was modeled using GOLD. For comparison, the E2 binding mode from mouse SULT1E1 is shown (light blue). B, superimposition of C traces of SULT1A1·PAP·pNP (pink) and SULT1A1·PAP·E2 (green). E2 is shown in orange. A loop (residues 84-90) that moves to accommodate E2 in the active site is highlighted in dark blue and indicated by an arrow.
Figure 4.
FIGURE 4. Stereoview comparing the binding modes of E2 (orange) bound to SULT1A1 and DHEA bound to SULT2A1. The productive or catalytic orientation of DHEA is shown in green, and the nonproductive orientation is in black. PAP (light blue) and the catalytic His108 (gray) of SULT1A1 are shown in a ball-and-stick representation.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 41482-41486) copyright 2005.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20304798 G.B.Cole, G.Keum, J.Liu, G.W.Small, N.Satyamurthy, V.Kepe, and J.R.Barrio (2010).
Specific estrogen sulfotransferase (SULT1E1) substrates and molecular imaging probe candidates.
  Proc Natl Acad Sci U S A, 107, 6222-6227.  
20235827 O.Khersonsky, and D.S.Tawfik (2010).
Enzyme promiscuity: a mechanistic and evolutionary perspective.
  Annu Rev Biochem, 79, 471-505.  
19250196 J.R.Pasqualini (2009).
Estrogen sulfotransferases in breast and endometrial cancers.
  Ann N Y Acad Sci, 1155, 88-98.  
19648114 J.Ziegler, W.Brandt, R.Geissler, and P.J.Facchini (2009).
Removal of substrate inhibition and increase in maximal velocity in the short chain dehydrogenase/reductase salutaridine reductase involved in morphine biosynthesis.
  J Biol Chem, 284, 26758-26767.  
18430142 G.E.Townsend, and D.H.Keating (2008).
Identification and characterization of KpsS, a novel polysaccharide sulphotransferase in Mesorhizobium loti.
  Mol Microbiol, 68, 1149-1164.  
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
17039368 F.Marsolais, J.Boyd, Y.Paredes, A.M.Schinas, M.Garcia, S.Elzein, and L.Varin (2007).
Molecular and biochemical characterization of two brassinosteroid sulfotransferases from Arabidopsis, AtST4a (At2g14920) and AtST1 (At2g03760).
  Planta, 225, 1233-1244.  
17110154 N.Hempel, N.Gamage, J.L.Martin, and M.E.McManus (2007).
Human cytosolic sulfotransferase SULT1A1.
  Int J Biochem Cell Biol, 39, 685-689.  
16804942 L.Dombrovski, A.Dong, A.Bochkarev, and A.N.Plotnikov (2006).
Crystal structures of human sulfotransferases SULT1B1 and SULT1C1 complexed with the cofactor product adenosine-3'- 5'-diphosphate (PAP).
  Proteins, 64, 1091-1094.
PDB codes: 1xv1 2etg 2z5f 3bfx
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.