Crystal structure of sulfotransferase STF9 from Mycobacterium avium

Md Murad Hossain, Yuuji Moriizumi, Shotaro Tanaka, Makoto Kimura, Yoshimitsu Kakuta

Research output: Contribution to journalArticle

Abstract

Sulfotransferases catalyze the sulfate conjugation of a wide variety of endogenous and exogenous molecules. Human pathogenic mycobacteria produce numerous sulfated molecules including sulfolipids which are well related to the virulence of several strains. The genome of Mycobacterium avium encodes eight putative sulfotransferases (stf1, stf4-stf10). Among them, STF9 shows higher similarity to human heparan sulfate 3-O-sulfotransferase isoforms than to the bacterial STs. Here, we determined the crystal structure of sulfotransferase STF9 in complex with a sulfate ion and palmitic acid at a resolution of 2.6 Å. STF9 has a spherical structure utilizing the classical sulfotransferase fold. STF9 exclusively possesses three N-terminal α-helices (α1, α2, α3) parallel to the 3′-phosphoadenosine-5′-phosphosulfate (PAPS) binding motif. The sulfate ion binds to the PAPS binding structural motif and the palmitic acid molecule binds in the deep cleft of the predicted substrate binding site suggesting the nature of endogenous acceptor substrate of STF9 resembles palmitic acid. The substrate binding site is covered by a flexible loop which may have involvement in endogenous substrate recognition. Based on the mutational study (Hossain et al., Mol Cell Biochem 350:155-162; 2011) and structural resemblance of STF9-sulfate ion-palmitic acid complex to the hHS3OST3 complex with PAP (3′-phosphoadenosine-5′-phosphate) and an acceptor sugar chain, Glu170 and Arg96 are appeared to be catalytic residues in STF9 sulfuryl transfer mechanism.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalMolecular and Cellular Biochemistry
DOIs
Publication statusAccepted/In press - 2011

Fingerprint

Sulfotransferases
Mycobacterium avium
Palmitic Acid
Crystal structure
Sulfates
Phosphoadenosine Phosphosulfate
Substrates
Ions
Molecules
Binding Sites
Heparitin Sulfate
Mycobacterium
Sugars
Virulence
Protein Isoforms
Genes
Genome

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Hossain, M. M., Moriizumi, Y., Tanaka, S., Kimura, M., & Kakuta, Y. (Accepted/In press). Crystal structure of sulfotransferase STF9 from Mycobacterium avium. Molecular and Cellular Biochemistry, 1-8. https://doi.org/10.1007/s11010-011-1093-x

Crystal structure of sulfotransferase STF9 from Mycobacterium avium. / Hossain, Md Murad; Moriizumi, Yuuji; Tanaka, Shotaro; Kimura, Makoto; Kakuta, Yoshimitsu.

In: Molecular and Cellular Biochemistry, 2011, p. 1-8.

Research output: Contribution to journalArticle

Hossain, Md Murad ; Moriizumi, Yuuji ; Tanaka, Shotaro ; Kimura, Makoto ; Kakuta, Yoshimitsu. / Crystal structure of sulfotransferase STF9 from Mycobacterium avium. In: Molecular and Cellular Biochemistry. 2011 ; pp. 1-8.
@article{ab2e2ac3ec244f5786ac669ccc1dcc0d,
title = "Crystal structure of sulfotransferase STF9 from Mycobacterium avium",
abstract = "Sulfotransferases catalyze the sulfate conjugation of a wide variety of endogenous and exogenous molecules. Human pathogenic mycobacteria produce numerous sulfated molecules including sulfolipids which are well related to the virulence of several strains. The genome of Mycobacterium avium encodes eight putative sulfotransferases (stf1, stf4-stf10). Among them, STF9 shows higher similarity to human heparan sulfate 3-O-sulfotransferase isoforms than to the bacterial STs. Here, we determined the crystal structure of sulfotransferase STF9 in complex with a sulfate ion and palmitic acid at a resolution of 2.6 {\AA}. STF9 has a spherical structure utilizing the classical sulfotransferase fold. STF9 exclusively possesses three N-terminal α-helices (α1, α2, α3) parallel to the 3′-phosphoadenosine-5′-phosphosulfate (PAPS) binding motif. The sulfate ion binds to the PAPS binding structural motif and the palmitic acid molecule binds in the deep cleft of the predicted substrate binding site suggesting the nature of endogenous acceptor substrate of STF9 resembles palmitic acid. The substrate binding site is covered by a flexible loop which may have involvement in endogenous substrate recognition. Based on the mutational study (Hossain et al., Mol Cell Biochem 350:155-162; 2011) and structural resemblance of STF9-sulfate ion-palmitic acid complex to the hHS3OST3 complex with PAP (3′-phosphoadenosine-5′-phosphate) and an acceptor sugar chain, Glu170 and Arg96 are appeared to be catalytic residues in STF9 sulfuryl transfer mechanism.",
author = "Hossain, {Md Murad} and Yuuji Moriizumi and Shotaro Tanaka and Makoto Kimura and Yoshimitsu Kakuta",
year = "2011",
doi = "10.1007/s11010-011-1093-x",
language = "English",
pages = "1--8",
journal = "Molecular and Cellular Biochemistry",
issn = "0300-8177",
publisher = "Springer Netherlands",

}

TY - JOUR

T1 - Crystal structure of sulfotransferase STF9 from Mycobacterium avium

AU - Hossain, Md Murad

AU - Moriizumi, Yuuji

AU - Tanaka, Shotaro

AU - Kimura, Makoto

AU - Kakuta, Yoshimitsu

PY - 2011

Y1 - 2011

N2 - Sulfotransferases catalyze the sulfate conjugation of a wide variety of endogenous and exogenous molecules. Human pathogenic mycobacteria produce numerous sulfated molecules including sulfolipids which are well related to the virulence of several strains. The genome of Mycobacterium avium encodes eight putative sulfotransferases (stf1, stf4-stf10). Among them, STF9 shows higher similarity to human heparan sulfate 3-O-sulfotransferase isoforms than to the bacterial STs. Here, we determined the crystal structure of sulfotransferase STF9 in complex with a sulfate ion and palmitic acid at a resolution of 2.6 Å. STF9 has a spherical structure utilizing the classical sulfotransferase fold. STF9 exclusively possesses three N-terminal α-helices (α1, α2, α3) parallel to the 3′-phosphoadenosine-5′-phosphosulfate (PAPS) binding motif. The sulfate ion binds to the PAPS binding structural motif and the palmitic acid molecule binds in the deep cleft of the predicted substrate binding site suggesting the nature of endogenous acceptor substrate of STF9 resembles palmitic acid. The substrate binding site is covered by a flexible loop which may have involvement in endogenous substrate recognition. Based on the mutational study (Hossain et al., Mol Cell Biochem 350:155-162; 2011) and structural resemblance of STF9-sulfate ion-palmitic acid complex to the hHS3OST3 complex with PAP (3′-phosphoadenosine-5′-phosphate) and an acceptor sugar chain, Glu170 and Arg96 are appeared to be catalytic residues in STF9 sulfuryl transfer mechanism.

AB - Sulfotransferases catalyze the sulfate conjugation of a wide variety of endogenous and exogenous molecules. Human pathogenic mycobacteria produce numerous sulfated molecules including sulfolipids which are well related to the virulence of several strains. The genome of Mycobacterium avium encodes eight putative sulfotransferases (stf1, stf4-stf10). Among them, STF9 shows higher similarity to human heparan sulfate 3-O-sulfotransferase isoforms than to the bacterial STs. Here, we determined the crystal structure of sulfotransferase STF9 in complex with a sulfate ion and palmitic acid at a resolution of 2.6 Å. STF9 has a spherical structure utilizing the classical sulfotransferase fold. STF9 exclusively possesses three N-terminal α-helices (α1, α2, α3) parallel to the 3′-phosphoadenosine-5′-phosphosulfate (PAPS) binding motif. The sulfate ion binds to the PAPS binding structural motif and the palmitic acid molecule binds in the deep cleft of the predicted substrate binding site suggesting the nature of endogenous acceptor substrate of STF9 resembles palmitic acid. The substrate binding site is covered by a flexible loop which may have involvement in endogenous substrate recognition. Based on the mutational study (Hossain et al., Mol Cell Biochem 350:155-162; 2011) and structural resemblance of STF9-sulfate ion-palmitic acid complex to the hHS3OST3 complex with PAP (3′-phosphoadenosine-5′-phosphate) and an acceptor sugar chain, Glu170 and Arg96 are appeared to be catalytic residues in STF9 sulfuryl transfer mechanism.

UR - http://www.scopus.com/inward/record.url?scp=80053348819&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80053348819&partnerID=8YFLogxK

U2 - 10.1007/s11010-011-1093-x

DO - 10.1007/s11010-011-1093-x

M3 - Article

SP - 1

EP - 8

JO - Molecular and Cellular Biochemistry

JF - Molecular and Cellular Biochemistry

SN - 0300-8177

ER -