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Transferase PDB id
Protein chains
239 a.a. *
243 a.a. *
TRE ×4
Waters ×410
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Mycobacterium smegmatis stf0 sulfotransferase with trehalose
Structure: Stf0 sulfotransferase. Chain: a, b, c, d. Engineered: yes
Source: Mycobacterium smegmatis. Organism_taxid: 1772. Gene: stf0. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Biol. unit: Dimer (from PQS)
2.60Å     R-factor:   0.220     R-free:   0.274
Authors: J.D.Mougous,C.J.Petzold,R.H.Senaratne,D.H.Lee,D.L.Akey,F.L.L S.E.Munchel,M.R.Pratt,L.W.Riley,J.A.Leary,J.M.Berger,C.R.Be
Key ref:
J.D.Mougous et al. (2004). Identification, function and structure of the mycobacterial sulfotransferase that initiates sulfolipid-1 biosynthesis. Nat Struct Mol Biol, 11, 721-729. PubMed id: 15258569 DOI: 10.1038/nsmb802
25-May-04     Release date:   20-Jul-04    
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Protein chain
Pfam   ArchSchema ?
P84151  (P84151_MYCSM) -  Sulfotransferase
267 a.a.
239 a.a.*
Protein chains
Pfam   ArchSchema ?
P84151  (P84151_MYCSM) -  Sulfotransferase
267 a.a.
243 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)


DOI no: 10.1038/nsmb802 Nat Struct Mol Biol 11:721-729 (2004)
PubMed id: 15258569  
Identification, function and structure of the mycobacterial sulfotransferase that initiates sulfolipid-1 biosynthesis.
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, C.R.Bertozzi.
Sulfolipid-1 (SL-1) is an abundant sulfated glycolipid and potential virulence factor found in Mycobacterium tuberculosis. SL-1 consists of a trehalose-2-sulfate (T2S) disaccharide elaborated with four lipids. We identified and characterized a conserved mycobacterial sulfotransferase, Stf0, which generates the T2S moiety of SL-1. Biochemical studies demonstrated that the enzyme requires unmodified trehalose as substrate and is sensitive to small structural perturbations of the disaccharide. Disruption of stf0 in Mycobacterium smegmatis and M. tuberculosis resulted in the loss of T2S and SL-1 formation, respectively. The structure of Stf0 at a resolution of 2.6 A reveals the molecular basis of trehalose recognition and a unique dimer configuration that encloses the substrate into a bipartite active site. These data provide strong evidence that Stf0 carries out the first committed step in the biosynthesis of SL-1 and establish a system for probing the role of SL-1 in M. tuberculosis infection.
  Selected figure(s)  
Figure 5.
Figure 5. Interactions between trehalose and Stf0. (a) Stereo diagram of representative Stf0 protein side chain and trehalose electron density shown in a composite simulated annealed omit map calculated with 2F[o] - F[c] coefficients and contoured at 1 . (b) Schematic of the interactions between one trehalose molecule and both protomers of the Stf0 dimer. Nitrogen and oxygen atoms are blue and red spheres, respectively. Water molecules are asterisks. Hydrogen bonds are dashed lines and hydrophobic interactions are semicircles. Glu33 and Pro93 (boxed) are contributed by the other protomer. For a table containing the lengths of all hydrogen bonds shown in this figure or discussed in the text, see Supplementary Table 2 online. (c) Stereo view of the Stf0 active site with modeled PAPS. C traces of the two protomers are blue and green tubes. Aside from the addition of the 5' PSB residue Arg15 and the removal of Pro93, residues represented as sticks are the same as those detailed in a. Hydrogen bonds are dashed lines and water molecules are gray spheres. PAPS was modeled based solely on a superposition of an EST -PAPS complex and Stf0. A pink dashed line shows the close proximity of the PAPS sulfur atom (orange) to the 2-OH group of Glc-A.
Figure 6.
Figure 6. Proposed biosynthesis of sulfolipid-1. The biosynthesis of SL-1 is initiated by sulfation of trehalose by Stf0 (step 1). Next, T2S is acylated with a saturated fatty acid group and a hydroxyphthioceranic acid group (HPA), forming SL[1278] (steps 2 and 3; unknown order). The dashed line indicates that the position of HPA on SL[1278] is uncertain26, 27, 29. Gilleron et al.27 propose a structure in which HPA occurs at the 3'-OH of Glc-B whereas the structure of SL-1 proposed by Goren et al.69 implies that the HPA group of SL[1278] occurs on the 6- or 6'-position. SL[1278] is next transported across the plasma membrane by MmpL8 (step 4). After transport by MmpL8, the biosynthesis of SL-1 is completed by acylation of SL[1278] with a phthioceranic acid group and another HPA group (steps 5 and 6; unknown order). Aspects of the pathway are reviewed in ref. 70.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2004, 11, 721-729) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21188624 M.M.Hossain, Y.Moriizumi, S.Tanaka, M.Kimura, and Y.Kakuta (2011).
Molecular cloning, expression, and functional analysis of a predicted sulfotransferase STF9 from Mycobacterium avium.
  Mol Cell Biochem, 350, 155-162.  
20160128 C.Bertozzi, and C.Bertozzi (2010).
Profile of Carolyn Bertozzi. Interview by Tinsley Davis.
  Proc Natl Acad Sci U S A, 107, 2737-2739.  
20136513 G.Malojcić, and R.Glockshuber (2010).
The PAPS-independent aryl sulfotransferase and the alternative disulfide bond formation system in pathogenic bacteria.
  Antioxid Redox Signal, 13, 1247-1259.  
  19729090 D.Kaur, M.E.Guerin, H.Skovierová, P.J.Brennan, and M.Jackson (2009).
Chapter 2: Biogenesis of the cell wall and other glycoconjugates of Mycobacterium tuberculosis.
  Adv Appl Microbiol, 69, 23-78.  
19276083 S.K.Hatzios, M.W.Schelle, C.M.Holsclaw, C.R.Behrens, Z.Botyanszki, F.L.Lin, B.L.Carlson, P.Kumar, J.A.Leary, and C.R.Bertozzi (2009).
PapA3 Is an Acyltransferase Required for Polyacyltrehalose Biosynthesis in Mycobacterium tuberculosis.
  J Biol Chem, 284, 12745-12751.  
18173284 C.D.Leigh, and C.R.Bertozzi (2008).
Synthetic studies toward Mycobacterium tuberculosis sulfolipid-I.
  J Org Chem, 73, 1008-1017.  
  18928249 C.M.Holsclaw, K.M.Sogi, S.A.Gilmore, M.W.Schelle, M.D.Leavell, C.R.Bertozzi, and J.A.Leary (2008).
Structural characterization of a novel sulfated menaquinone produced by stf3 from Mycobacterium tuberculosis.
  ACS Chem Biol, 3, 619-624.  
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.  
19036922 G.Malojcić, R.L.Owen, J.P.Grimshaw, M.S.Brozzo, H.Dreher-Teo, and R.Glockshuber (2008).
A structural and biochemical basis for PAPS-independent sulfuryl transfer by aryl sulfotransferase from uropathogenic Escherichia coli.
  Proc Natl Acad Sci U S A, 105, 19217-19222.
PDB codes: 3elq 3ets 3ett
18625336 P.Bojarová, and S.J.Williams (2008).
Sulfotransferases, sulfatases and formylglycine-generating enzymes: a sulfation fascination.
  Curr Opin Chem Biol, 12, 573-581.  
18505396 R.Goude, and T.Parish (2008).
The genetics of cell wall biosynthesis in Mycobacterium tuberculosis.
  Future Microbiol, 3, 299-313.  
18454554 S.K.Hatzios, A.T.Iavarone, and C.R.Bertozzi (2008).
Rv2131c from Mycobacterium tuberculosis is a CysQ 3'-phosphoadenosine-5'-phosphatase.
  Biochemistry, 47, 5823-5831.  
17521419 D.J.Beste, T.Hooper, G.Stewart, B.Bonde, C.Avignone-Rossa, M.E.Bushell, P.Wheeler, S.Klamt, A.M.Kierzek, and J.McFadden (2007).
GSMN-TB: a web-based genome-scale network model of Mycobacterium tuberculosis metabolism.
  Genome Biol, 8, R89.  
17559818 F.L.Lin, H.van Halbeek, and C.R.Bertozzi (2007).
Synthesis of mono- and dideoxygenated alpha,alpha-trehalose analogs.
  Carbohydr Res, 342, 2014-2030.  
17592143 P.Kumar, M.W.Schelle, M.Jain, F.L.Lin, C.J.Petzold, M.D.Leavell, J.A.Leary, J.S.Cox, and C.R.Bertozzi (2007).
PapA1 and PapA2 are acyltransferases essential for the biosynthesis of the Mycobacterium tuberculosis virulence factor sulfolipid-1.
  Proc Natl Acad Sci U S A, 104, 11221-11226.  
17389997 R.S.Gokhale, P.Saxena, T.Chopra, and D.Mohanty (2007).
Versatile polyketide enzymatic machinery for the biosynthesis of complex mycobacterial lipids.
  Nat Prod Rep, 24, 267-277.  
17329243 R.Shi, S.S.Lamb, S.Bhat, T.Sulea, G.D.Wright, A.Matte, and M.Cygler (2007).
Crystal structure of StaL, a glycopeptide antibiotic sulfotransferase from Streptomyces toyocaensis.
  J Biol Chem, 282, 13073-13086.
PDB codes: 2ov8 2ovb 2ovf
16387658 J.D.Mougous, D.H.Lee, S.C.Hubbard, M.W.Schelle, D.J.Vocadlo, J.M.Berger, and C.R.Bertozzi (2006).
Molecular basis for G protein control of the prokaryotic ATP sulfurylase.
  Mol Cell, 21, 109-122.
PDB code: 1zun
16537518 J.D.Mougous, R.H.Senaratne, C.J.Petzold, M.Jain, D.H.Lee, M.W.Schelle, M.D.Leavell, J.S.Cox, J.A.Leary, L.W.Riley, and C.R.Bertozzi (2006).
A sulfated metabolite produced by stf3 negatively regulates the virulence of Mycobacterium tuberculosis.
  Proc Natl Acad Sci U S A, 103, 4258-4263.  
16933356 M.W.Schelle, and C.R.Bertozzi (2006).
Sulfate metabolism in mycobacteria.
  Chembiochem, 7, 1516-1524.  
16553880 R.H.Senaratne, A.D.De Silva, S.J.Williams, J.D.Mougous, J.R.Reader, T.Zhang, S.Chan, B.Sidders, D.H.Lee, J.Chan, C.R.Bertozzi, and L.W.Riley (2006).
5'-Adenosinephosphosulphate reductase (CysH) protects Mycobacterium tuberculosis against free radicals during chronic infection phase in mice.
  Mol Microbiol, 59, 1744-1753.  
16232291 E.Vanbleu, B.P.Choudhury, R.W.Carlson, and J.Vanderleyden (2005).
The nodPQ genes in Azospirillum brasilense Sp7 are involved in sulfation of lipopolysaccharides.
  Environ Microbiol, 7, 1769-1774.  
16204525 H.J.Tobias, M.P.Schafer, M.Pitesky, D.P.Fergenson, J.Horn, M.Frank, and E.E.Gard (2005).
Bioaerosol mass spectrometry for rapid detection of individual airborne Mycobacterium tuberculosis H37Ra particles.
  Appl Environ Microbiol, 71, 6086-6095.  
15280877 S.J.Williams, and G.J.Davies (2004).
A master of its sulfate.
  Nat Struct Mol Biol, 11, 686-687.  
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.