SufE

SufE (PF3D7_0206100) is an apicoplast-localized cysteine desulfuration protein of Plasmodium falciparum that serves as the sulfur-transfer partner in the first, sulfur-acquisition step of the apicoplast SUF pathway for Fe-S cluster biosynthesis (PMID:24086138, PMID:24709262). It localizes exclusively to the apicoplast and forms an in vivo complex with the cysteine desulfurase SufS (PfSufS), greatly enhancing SufS enzymatic activity; structural modeling positions conserved cysteine residues of the two proteins in proximity, consistent with sulfide transfer from the PLP-bound active site of SufS to SufE (PMID:24709262). This SufSE partnership is conserved across Plasmodium species: in P. vivax clinical-isolate proteins, the SufSE complex mobilizes sulfur that is subsequently assembled onto the scaffold protein PvSufA in vitro (PMID:30721667). The pathway is essential for blood-stage survival, as targeted deletion of the SufE ortholog in P. berghei was refractory (PMID:24586983). Beyond its established partnership with SufS in the sulfur-acquisition step, SufE has not been independently characterized in the available corpus; the downstream apicoplast-maintenance functions of sulfur mobilization (Fe-S assembly and MnmA-dependent tRNA modification) have been attributed to SufS rather than to SufE itself (PMID:37166116).

1. 2013 Medium

   Establishing where SufE acts and whether it participates in sulfur acquisition answered whether the parasite's SUF pathway operates in the apicoplast and identified SufE as SufS's functional partner.

   Evidence Subcellular localization and complementation assay demonstrating SufS cysteine desulfurase activity in P. falciparum

   PMID:24086138

   Open questions at the time

   • Did not resolve the biochemical mechanism of sulfur transfer between SufE and SufS
   • No direct measurement of SufE's effect on SufS kinetics
2. 2014 High

   Whether SufE physically partners SufS in vivo and how it contributes catalytically was resolved by showing complex formation and enhancement of desulfurase activity, defining SufE as an activator of sulfide mobilization.

   Evidence In vivo Co-immunoprecipitation, in vitro cysteine desulfurase activity assay, localization, and structural modeling in P. falciparum

   PMID:24709262

   Open questions at the time

   • Structural model of the cysteine-to-cysteine sulfide relay not experimentally confirmed by a solved structure
   • Stoichiometry and dynamics of the SufSE complex not defined
3. 2014 Medium

   Whether SufE is genetically essential was addressed in P. berghei, where refractory deletion established the sulfur-acquisition step as indispensable for asexual blood-stage growth.

   Evidence Targeted gene deletion and endogenous fluorescent tagging in P. berghei

   PMID:24586983

   Open questions at the time

   • Refractory deletion does not distinguish which downstream function (Fe-S assembly vs other) drives essentiality
   • No conditional knockdown to define the terminal phenotype of SufE loss
4. 2019 Medium

   Whether the SufSE sulfur-transfer mechanism is conserved and feeds a downstream scaffold was tested in P. vivax, showing the SufSE complex mobilizes sulfur that assembles onto SufA.

   Evidence In vitro protein interaction and Fe-S cluster assembly assays using P. vivax clinical-isolate proteins

   PMID:30721667

   Open questions at the time

   • In vitro reconstitution using clinical-isolate material adds variability and does not establish in vivo flux
   • SufE's specific contribution to SufA loading not isolated from SufS
5. 2023 Low

   Whether the sulfur-acquisition step has functions beyond Fe-S biosynthesis was examined via SufS, revealing a dual role including MnmA-dependent tRNA modification for apicoplast maintenance, with SufE implied as the upstream partner but not independently dissected.

   Evidence Conditional deletion (chemical bypass), organelle and genome integrity assays, and complementation with bacterial MnmA and cognate desulfurase in P. falciparum

   PMID:37166116

   Open questions at the time

   • SufE (PF3D7_0206100) itself was not independently characterized in this study beyond its partnership with SufS
   • Whether SufE contributes specifically to the MnmA-directed sulfur branch is untested
   • No SufE-specific conditional deletion phenotype reported

• The independent, SufE-specific determinants of sulfur-transfer selectivity — whether SufE channels sulfur preferentially toward Fe-S assembly versus MnmA-dependent tRNA thiolation — remain unresolved.
• No SufE conditional knockdown defining the terminal phenotype
• No solved SufSE structure confirming the modeled sulfide relay
• SufE's partitioning between downstream sulfur-acceptor pathways unmeasured