Escherichia coli SufE Sulfur Transfer Protein Modulates the SufS Cysteine Desulfurase through Allosteric Conformational Dynamics

Singh, Harsimran; Dai, Yuyuan; Outten, F. Wayne; Busenlehner, Laura S.

doi:10.1074/jbc.m113.525709

Cited by 39 publications

(91 citation statements)

References 35 publications

(86 reference statements)

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“…In group I, the long extended lobe is sufficiently flexible to transfer the sulfur moiety to the biological partner, which does not need flexibility. Recent studies show that this is opposite to the case in group II CDs (Kim & Park, 2013;Singh et al, 2013). Indeed, in the latter a -hairpin constrains the enzyme active site in a 'closed conformation'.…”

Section: Resultsmentioning

confidence: 70%

“…4; Kim & Park, 2013) and by deuterium-exchange experiments for SufS-SufE (Singh et al, 2013). These studies revealed that the conformation of the CD alone and in complex with the sulfurtransferase was similar.…”

Section: Atsufe1 Modelmentioning

confidence: 62%

“…These studies revealed that the conformation of the CD alone and in complex with the sulfurtransferase was similar. In contrast, the sulfur-accepting cysteine of CsdE (or SufE) was buried in a hydrophobic cavity in the free enzyme and was out of the groove in an exposed conformation suitable for sulfur capture (Kim & Park, 2013;Singh et al, 2013). We attempted to build a model of AtNfs2-SufE AtSufE1 (Fig.…”

Section: Atsufe1 Modelmentioning

confidence: 99%

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X-ray structures of Nfs2, the plastidial cysteine desulfurase fromArabidopsis thaliana

et al. 2014

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The chloroplastic Arabidopsis thaliana Nfs2 (AtNfs2) is a group II pyridoxal 5 0 -phosphate-dependent cysteine desulfurase that is involved in the initial steps of iron-sulfur cluster biogenesis. The group II cysteine desulfurases require the presence of sulfurtransferases such as SufE proteins for optimal activity. Compared with group I cysteine desulfurases, proteins of this group contains a smaller extended lobe harbouring the catalytic cysteine and have a -hairpin constraining the active site. Here, two crystal structures of AtNfs2 are reported: a wild-type form with the catalytic cysteine in a persulfide-intermediate state and a C384S variant mimicking the resting state of the enzyme. In both structures the well conserved Lys241 covalently binds pyridoxal 5 0 -phosphate, forming an internal aldimine. Based on available homologous bacterial complexes, a model of a complex between AtNfs2 and the SufE domain of its biological partner AtSufE1 is proposed, revealing the nature of the binding sites.

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Section: Resultsmentioning

confidence: 70%

Section: Atsufe1 Modelmentioning

confidence: 62%

Section: Atsufe1 Modelmentioning

confidence: 99%

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X-ray structures of Nfs2, the plastidial cysteine desulfurase fromArabidopsis thaliana

et al. 2014

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“…Using hydrogen–deuterium exchange mass spectrometry (HDX-MS), we observed similar increases in the solvent accessibility of the SufE Cys51 loop upon interaction with SufS. 10 Together, these results indicate that the active conformation of SufE and its homologues is one where the active site Cys loop is flipped out of its hydrophobic groove into a more extended conformation.…”

mentioning

confidence: 66%

“…While the dynamics of SufS–SufE interactions have been intensively studied, the structure of the SufS–SufE complex and the molecular details of how SufS and SufE interact are not clear. 1–3,8–10 …”

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confidence: 99%

SufE D74R Substitution Alters Active Site Loop Dynamics To Further Enhance SufE Interaction with the SufS Cysteine Desulfurase

et al. 2015

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Many essential metalloproteins require iron–sulfur (Fe–S) cluster cofactors for their function. In vivo persulfide formation from L-cysteine is a key step in the biogenesis of Fe–S clusters in most organisms. In Escherichia coli, the SufS cysteine desulfurase mobilizes persulfide from L-cysteine via a PLP-dependent ping-pong reaction. SufS requires the SufE partner protein to transfer the persulfide to the SufB Fe–S cluster scaffold. Without SufE, the SufS enzyme fails to efficiently turn over and remains locked in the persulfide-bound state. Coordinated protein–protein interactions mediate sulfur transfer from SufS to SufE. Multiple studies have suggested that SufE must undergo a conformational change to extend its active site Cys loop during sulfur transfer from SufS. To test this putative model, we mutated SufE Asp74 to Arg (D74R) to increase the dynamics of the SufE Cys51 loop. Amide hydrogen/deuterium exchange mass spectrometry (HDX-MS) analysis of SufE D74R revealed an increase in solvent accessibility and dynamics in the loop containing the active site Cys51 used to accept persulfide from SufS. Our results indicate that the mutant protein has a stronger binding affinity for SufS than that of wild-type SufE. In addition, SufE D74R can still enhance SufS desulfurase activity and did not show saturation at higher SufE D74R concentrations, unlike wild-type SufE. These results show that dynamic changes may shift SufE to a sulfur-acceptor state that interacts more strongly with SufS.

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FeSCluster Assembly:SUFSystem in Bacteria, Plastids and Archaea

Dong

Witcher

Outten

et al. 2017

Encyclopedia of Inorganic and Bioinorganic Chemistry

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Iron–sulfur (Fe–S) clusters are essential cofactors in biology due to their use in critical pathways such as nitrogen fixation, photosynthesis, and respiration. Fe–S cluster biogenesis requires complex systems to mobilize iron and sulfide, assemble the nascent cluster, and target Fe–S clusters to downstream target proteins. All of these steps must be coordinated to protect Fe–S cluster biogenesis intermediates from reactive oxygen species and other stressors. Multiple Fe–S cluster biogenesis pathways exist in different organisms and organelles. The Suf ( su lfur f ormation) pathway is phylogenetically the most ancient of the cluster biogenesis systems and is distributed across all domains of life. It can be found as the primary Fe–S cluster biogenesis pathway or as an auxiliary pathway adapted to maintain Fe–S cluster metabolism under stress conditions. Here we describe the biochemical, genetic, and physiological characterization of the Suf system, in all of its iterations.

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Escherichia coli SufE Sulfur Transfer Protein Modulates the SufS Cysteine Desulfurase through Allosteric Conformational Dynamics

Cited by 39 publications

References 35 publications

X-ray structures of Nfs2, the plastidial cysteine desulfurase fromArabidopsis thaliana

X-ray structures of Nfs2, the plastidial cysteine desulfurase fromArabidopsis thaliana

SufE D74R Substitution Alters Active Site Loop Dynamics To Further Enhance SufE Interaction with the SufS Cysteine Desulfurase

FeSCluster Assembly:SUFSystem in Bacteria, Plastids and Archaea

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