Affinage · Plasmodium

SIR2A

PF3D7_1328800 · transcriptional regulatory protein sir2a

Annotated
2026-09-08
29 papers in source corpus 25 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SIR2A (PF3D7_1328800) is an NAD+-dependent sirtuin in Plasmodium that establishes and maintains heterochromatic gene silencing, functioning as a central link between epigenetic control of virulence and ribosomal genes and the parasite's metabolic state (PMID:15820676, PMID:19402747, PMID:41419483). At subtelomeric loci it nucleates a gradient of histone hypoacetylation that spreads >50 kb from telomeres into var virulence genes, and its removal from a var promoter accompanies gene activation; loss of SIR2A de-represses specific var subsets (biased to upsA/upsB/upsE), breaks mutually exclusive var expression, and lengthens telomeric repeats, establishing it as a required determinant of antigenic variation and telomere end protection (PMID:15820676, PMID:15820675, PMID:19402747, PMID:19666023). Biochemically, recombinant SIR2A deacetylates histone H3/H4 tails, is inhibited by nicotinamide, and preferentially removes medium/long-chain fatty acyl groups from lysines, indicating that de-fatty-acylation as well as deacetylation underlies its silencing function (PMID:17827348, PMID:21992006); its activity is enhanced by DNA and nucleosome binding and modulated by free fatty acids (PMID:39897407, PMID:39386451). Beyond telomeres, SIR2A also accumulates in the nucleolus where it silences rRNA genes and thereby tunes merozoite number and parasite multiplication rate, and it couples fluctuating intracellular NAD+ to rDNA de-repression during metabolic transitions (PMID:23443558, PMID:41419483). SIR2A additionally acts as a regulatory deacetylase toward non-histone partners: it deacetylates PfAlba3 at K23 to switch on its DNA-binding and nuclease activity (PMID:22006844, PMID:36947546), and in P. yoelii it deacetylates the guanylyl cyclase GCβ to drive its ookinete-extrados localization, gliding motility, and mosquito infectivity (PMID:40050296). Its expression and protein stability are controlled by PfHsp90, which chaperones SIR2A and, at febrile temperature, transcriptionally represses it to trigger var de-repression (PMID:33538363, PMID:36121150).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2005 High

    Established that SIR2A physically organizes subtelomeric heterochromatin and is required for silencing of var virulence genes, defining its role in antigenic variation.

    Evidence ChIP, immunofluorescence and genetic disruption in P. falciparum showing a telomeric hypoacetylation gradient and var de-repression on knockout

    PMID:15820675 PMID:15820676

    Open questions at the time
    • Enzymatic activity not yet demonstrated in vitro
    • Mechanism of chromatin spreading not resolved
  2. 2007 High

    Demonstrated that SIR2A is an enzyme, catalyzing NAD+-dependent histone deacetylation coupled to ADP-ribosylation, providing the molecular activity underlying silencing.

    Evidence In vitro assays with recombinant protein plus histone fractionation in P. falciparum

    PMID:17827348

    Open questions at the time
    • Physiological substrates in vivo not defined
    • Relationship of ADP-ribosylation to silencing in cells untested
  3. 2007 High

    Characterized the catalytic mechanism, oligomeric behavior, and NAD+ hydrolase chemistry of SIR2A, distinguishing parasite-specific features.

    Evidence Bisubstrate kinetics, size exclusion, terminal deletion mutagenesis, and stereochemical analysis of reaction products in vitro

    PMID:18221799 PMID:18729382

    Open questions at the time
    • Cellular relevance of NAD+-driven trimer-to-monomer transition unknown
    • In vivo significance of dual NAD+ glycohydrolase mechanisms untested
  4. 2008 Medium

    Extended the regulatory context of SIR2A by showing endogenous HDAC activity, sumoylation as a post-translational modification, and coordinated telomeric localization with PfOrc1.

    Evidence Western blot/HDAC assays, Co-IP/LC-MS/MS for PfSUMO, and IFA/ChIP/gel-shift for Orc1 co-association in P. falciparum

    PMID:18397290 PMID:18525026 PMID:18547337

    Open questions at the time
    • Functional consequence of SIR2A sumoylation not tested
    • Direct role of SIR2A in the Orc1 co-localization not directly assayed
  5. 2009 High

    Resolved which var subsets depend on SIR2A and showed it enforces mutually exclusive expression and telomeric end protection, quantifying its contribution to antigenic switching.

    Evidence Multiple independent knockout clones with microarray/RT-PCR, ChIP, telomere length assay, and surface protein detection in P. falciparum

    PMID:19402747 PMID:19666023

    Open questions at the time
    • Residual switching in absence of SIR2A implies redundant factors not identified
    • Distinction of promoter-type specificity mechanism incomplete
  6. 2011 Medium

    Redefined the biochemical basis of SIR2A silencing by revealing preferential de-fatty-acylation and identifying PfAlba3 as a non-histone substrate whose DNA binding is controlled by SIR2A.

    Evidence In vitro enzymology with fatty acyl-lysine and structural analysis; Co-IP, in vitro deacetylation and colocalization for PfAlba3; ChIP for H2A.Z antagonism in P. falciparum

    PMID:21379342 PMID:21992006 PMID:22006844

    Open questions at the time
    • In vivo balance of deacetylation versus de-fatty-acylation unquantified
    • How SIR2A antagonizes H2A.Z mechanistically unclear
  7. 2011 Medium

    Identified a structural zinc requirement for SIR2A folding and activity.

    Evidence Metal chelation, circular dichroism, zinc reconstitution and activity assays in vitro

    PMID:20601220

    Open questions at the time
    • Single study, single lab
    • Regulatory (versus purely structural) role of zinc in cells untested
  8. 2012 Medium

    Placed SIR2A upstream of ORC1 chromatin loading, establishing a reciprocal dependence governing subtelomeric var regulation.

    Evidence ChIP and IFA in SIR2A-deficient and ORC1 N-terminus overexpressing P. falciparum

    PMID:22379140

    Open questions at the time
    • Direct versus indirect interaction between SIR2A and ORC1 not defined
    • Single lab
  9. 2013 High

    Discovered a nucleolar role for SIR2A in rRNA gene silencing that regulates merozoite number and parasite multiplication, extending its function beyond var genes.

    Evidence Knockout, complementation, overexpression, ChIP at rDNA, rRNA RT-qPCR and merozoite counting in P. falciparum

    PMID:23443558

    Open questions at the time
    • Signal that partitions SIR2A between telomeres and nucleolus unknown
    • Connection between rRNA level and merozoite number mechanistically indirect
  10. 2016 Medium

    Confirmed the var-silencing role by complementation and implicated SIR2A in genome integrity.

    Evidence Knockout, complementation, var profiling and chromosomal analysis in P. falciparum 3D7

    PMID:25780929

    Open questions at the time
    • Incomplete complementation leaves quantitative role uncertain
    • Mechanism linking SIR2A loss to chromosomal rearrangement unresolved
  11. 2022 Medium

    Identified PfHsp90 as an upstream chaperone and transcriptional regulator that controls SIR2A protein stability and its temperature-responsive expression, linking heat stress to var de-repression.

    Evidence Co-IP, ChIP for H3K9me3 at the SIR2A promoter, pharmacological Hsp90 inhibition with HDAC/RT-qPCR readouts in P. falciparum

    PMID:33538363 PMID:36121150

    Open questions at the time
    • Direct effect of inhibitors on SIR2A versus broad chaperone loss hard to isolate
    • Single lab
  12. 2023 Medium

    Defined a specific molecular switch whereby SIR2A deacetylation of PfAlba3 K23 gates its DNA binding and nuclease activity.

    Evidence Co-IP, in vitro deacetylation, site-specific mass spectrometry and mutagenesis in P. falciparum

    PMID:36947546

    Open questions at the time
    • Downstream biological output of PfAlba3 nuclease switch in vivo unclear
    • Single lab
  13. 2024 High

    Showed that DNA/nucleosome context and free fatty acids act as endogenous regulators of SIR2A dual activities, and identified synthetic inhibitors.

    Evidence In vitro assays with nucleosome/DNA substrates, fatty acid supplementation, and compound library screening in P. falciparum

    PMID:39386451 PMID:39897407

    Open questions at the time
    • In vivo relevance of fatty-acid regulation untested
    • Cellular efficacy/specificity of inhibitors not established
  14. 2025 Medium

    Connected SIR2A activity to metabolic state, showing it couples NAD+ availability to rDNA silencing and, in P. yoelii, deacetylates GCβ to enable ookinete gliding and mosquito transmission.

    Evidence Metabolic perturbation with epigenetic readouts in P. falciparum; BioID, knockout, colocalization, in vivo deacetylation, NAD+ quantification and mosquito infection in P. yoelii

    PMID:40050296 PMID:41419483

    Open questions at the time
    • Whether GCβ regulation occurs in P. falciparum untested
    • Direct sensing of NAD+ by SIR2A versus indirect effects not fully separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how SIR2A is targeted to and partitioned between telomeric, nucleolar, and cytoplasmic/ookinete sites, and which of its deacetylase versus de-fatty-acylase activities dominates at each locus in vivo.
  • Recruitment mechanism to specific loci unknown
  • In vivo substrate spectrum incompletely mapped
  • Relative in vivo contribution of deacetylation versus de-fatty-acylation unquantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
GCΒ / GUANYLYL CYCLASE BETA IN P. YOELII (DEACETYLATED TO PROMOTE OES LOCALIZATION) [#21]PFALBA3 (DEACETYLATED AT K23 TO ENABLE DNA BINDING/NUCLEASE ACTIVITY) [#10, #19]PFHSP90 (CHAPERONE; STABILIZES AND TRANSCRIPTIONALLY REGULATES SIR2A) [#17, #18]PFORC1 (CO-ASSOCIATES AT TELOMERES; RECIPROCAL DEPENDENCE FOR SUBTELOMERIC LOADING) [#5, #15]PFSUMO (SIR2A IS A SUMOYLATION TARGET) [#4]

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 SIR2A (PfSir2) forms a chromosomal gradient of heterochromatin structure and histone hypoacetylation at telomeres, spreading >50 kb into telomere-proximal regions including var gene loci. Upon activation of a specific telomere-associated var gene, SIR2A is removed from the promoter region and histone acetylation occurs, demonstrating that mutually exclusive var gene transcription is linked to dynamic chromatin remodeling by SIR2A. Chromatin immunoprecipitation (ChIP), immunofluorescence, genetic disruption Cell High 15820676
2005 Genetic disruption of SIR2A (PfSIR2) results in activation of var genes that are normally silenced, demonstrating that SIR2A is required for var gene silencing through heterochromatic mechanisms. Gene disruption (knockout) with var gene expression analysis Cell High 15820675
2007 Recombinant SIR2A (PfSir2) efficiently deacetylates the N-terminal tails of histones H3 and H4 in vitro, and also catalyzes ADP-ribosylation of both histones and itself. The deacetylase activity of SIR2A is dependent on its ADP-ribosylation activity. SIR2A can be completely inhibited by nicotinamide. SIR2A co-fractionates with histones in blood-stage parasites. In vitro enzymatic assay with recombinant protein, histone deacetylase assay, ADP-ribosylation assay, protein fractionation Eukaryotic cell High 17827348
2009 SIR2A (PfSir2A) and PfSir2B are NAD+-dependent histone deacetylases required for silencing of different var gene subsets classified by their conserved promoter type. Parasites lacking SIR2A show breakdown of mutually exclusive var gene expression. SIR2A paralogues are involved in cis spreading of silenced chromatin from var gene promoters into adjacent regions. Parasites lacking SIR2A but not Sir2B have considerably longer telomeric repeats, demonstrating a role for SIR2A specifically in telomeric end protection. Gene disruption (knockout), microarray expression analysis, chromatin immunoprecipitation, telomere length analysis PLoS biology High 19402747
2008 SIR2A (PfSir2) is identified as a target for sumoylation (SUMO conjugation) by the P. falciparum SUMO orthologue PfSUMO, as demonstrated by co-immunoprecipitation and LC-MS/MS analysis. Co-immunoprecipitation, western blot with anti-PfSUMO antibodies, LC-MS/MS Cellular microbiology Medium 18547337
2008 SIR2A (PfSir2) and PfOrc1 both associate with telomeric clusters at the nuclear periphery and undergo coordinated subcellular reorganization prior to DNA replication, dissociating from telomere clusters and spreading into the nucleus and cytoplasm. Super gel-shift and ChIP show physical association of Orc1 with telomere repeats, and the data suggest that Orc1 cooperates with SIR2A in telomeric silencing. Immunofluorescence assay, chromatin immunoprecipitation, super gel-shift assay Journal of cell science Medium 18525026
2008 SIR2A (PfSir2) is a NAD+-dependent deacetylase that also acts as an NAD+ glycohydrolase through two distinct mechanisms: one acetyllysine-independent (alpha-stereochemistry, insensitive to nicotinamide) and one acetyllysine-dependent (beta-stereochemistry via an imidate intermediate, inhibited by nicotinamide). These findings establish novel enzymatic reactions of SIR2A and provide mechanistic insight into sirtuin-catalyzed ADP-ribosyl transfer. In vitro enzymatic assay, product stereochemistry determination using methanol solvolysis and NMR/chromatography Biochemistry High 18729382
2007 SIR2A (PfSir2) exhibits rapid equilibrium ordered sequential kinetic mechanism with peptide binding preceding NAD+. SIR2A forms trimers in solution (like yeast Sir2), but NAD+ causes dissociation of trimers to monomers (a feature unique to the parasite enzyme). The C-terminus mediates homotrimerization; N-terminal deletion reduces catalytic efficiency without altering substrate affinity. Deletion of both termini relaxes NAD+ specificity. Surfactin competitively inhibits SIR2A with respect to NAD+ and uncompetitively with respect to acetylated peptide. Bisubstrate kinetic analysis, size exclusion chromatography, N- and C-terminal deletion mutagenesis, enzyme inhibition assays Molecular and biochemical parasitology High 18221799
2008 SIR2A (PfSir2) HDAC activity is present in blood-stage parasites as confirmed by specific antibodies detecting the endogenous ~30 kDa protein, and this activity can be inhibited by nicotinamide. Western blot with specific antibodies, in vitro HDAC activity assay, nicotinamide inhibition FEMS microbiology letters Medium 18397290
2011 SIR2A (PfSir2A) preferentially hydrolyzes medium and long chain fatty acyl groups from lysine residues rather than acetyl groups, as supported by enzymology and structural evidence. P. falciparum proteins contain such fatty acyl lysine modifications that can be removed by purified SIR2A in vitro, suggesting that the physiological function of SIR2A in antigen variation may be achieved via de-fatty-acylation rather than deacetylation. In vitro enzymatic assay with recombinant protein, structural analysis, mass spectrometry of parasite protein fatty acyl-lysine modifications ACS chemical biology High 21992006
2011 SIR2A (PfSir2A, a nuclear localized deacetylase) physically interacts with PfAlba3 and deacetylates the lysine residue of the N-terminal peptide of PfAlba3 that is specific for DNA binding. SIR2A co-localizes with PfAlba3 at the periphery of the nucleus. Co-immunoprecipitation, in vitro deacetylation assay, immunofluorescence colocalization Nucleic acids research Medium 22006844
2010 SIR2A (PfSir2) contains a non-catalytic zinc ion coordinated by cysteine thiol groups. Zinc removal causes partial structural collapse and loss of activity; zinc reconstitution of apo-SIR2A restores both structure and activity, demonstrating reversible zinc binding as a structural requirement for enzyme function. Metal chelation, circular dichroism/structural assay, zinc reconstitution, enzyme activity assay Biochimica et biophysica acta Medium 20601220
2013 SIR2A accumulates in the nucleolus in addition to telomeric regions. In parasites with disrupted SIR2A, histones near the transcription start sites of all ribosomal RNA genes are hyperacetylated and rRNA gene transcription is upregulated. Complementation of SIR2A-disrupted parasites restores rRNA levels; SIR2A overexpression decreases rRNA synthesis. SIR2A modulation of rRNA synthesis is linked to altered numbers of daughter merozoites and parasite multiplication rate. Gene disruption (knockout), complementation, overexpression, ChIP for histone acetylation at rDNA loci, RT-qPCR for rRNA levels, merozoite counting Nature communications High 23443558
2009 SIR2A (PfSIR2A) knockout parasites activate ~10 specific var genes in every independent clone, biased toward upsA, upsBA, and upsE var gene subclasses, with 2–3 fold higher total var transcript levels than wildtype. At least one activated transcript (VAR2CSA) is translated and expressed on the infected cell surface. In the absence of SIR2A, antigenic switching over time is diminished but not abolished. Multiple independent SIR2A knockout clones, quantitative RT-PCR, var gene expression profiling, flow cytometry/surface protein detection International journal for parasitology High 19666023
2011 In immature parasites lacking SIR2A, high var transcription levels correlate with enrichment of histone variant PfH2A.Z at the TSS of var genes. As SIR2A knockout parasites mature, var genes are silenced but PfH2A.Z remains enriched at var gene TSS (in contrast to SIR2B KO where PfH2A.Z is lost from the TSS of de-repressed var genes in mature parasites), indicating that PfH2A.Z occupancy at the active var promoter is antagonized by SIR2A during the intraerythrocytic life cycle. Chromatin immunoprecipitation (ChIP) in SIR2A and SIR2B knockout parasites at multiple life cycle stages PLoS pathogens Medium 21379342
2012 Binding and propagation of PfORC1 to telomeric and subtelomeric regions was severely compromised in SIR2A-deficient parasites, suggesting dependence of endogenous ORC1 on SIR2A for var gene regulation. Conversely, overexpression of the ORC1 N-terminus compromises SIR2A binding at subtelomeric loci and var gene promoters, consistent with de-repression of some var genes. ChIP in SIR2A-deficient and ORC1-overexpressing parasites, immunofluorescence Nucleic acids research Medium 22379140
2015 Complementation of SIR2A genetic disruption in P. falciparum 3D7 resulted in a significant decrease in previously elevated var gene expression levels but with continued expression of multiple var genes, confirming the role of SIR2A in var gene regulation but indicating incomplete restoration. Rearranged chromosomes were observed in the 3D7 SIR2A knockout line, implicating SIR2A in maintenance of genome integrity. Gene disruption (knockout), complementation, var gene expression profiling, chromosomal analysis PloS one Medium 25780929
2021 PfHsp90 physically occupies SIR2A promoter proximal regions, recruits H3K9me3 (conferring a heterochromatic state), and thereby transcriptionally downregulates SIR2A at the mid-ring stage in response to febrile temperature. Reduced SIR2A occupancy at sub-telomeric var promoters under these conditions leads to de-repression of var genes. PfHsp90 inhibitors (17-AAG or Radicicol) reverse the transcriptional downregulation of SIR2A. ChIP for PfHsp90 and H3K9me3 at SIR2A promoter, RT-qPCR, pharmacological inhibition of PfHsp90 Molecular microbiology Medium 33538363
2022 PfHsp90 physically interacts with SIR2A protein and acts as a chaperone required for its stability and maturation. Inhibition of PfHsp90 activity (via 17-AAG or Radicicol) results in depletion of SIR2A protein and loss of its histone deacetylase activity, leading to de-repression of var genes and loss of ribosomal silencing. Co-immunoprecipitation of PfHsp90 with SIR2A, pharmacological inhibition of PfHsp90, western blot for SIR2A protein levels, HDAC activity assay, RT-qPCR for var and rRNA mSphere Medium 36121150
2023 SIR2A interacts with PfAlba3 and deacetylates K23-acetylated PfAlba3, enabling its DNA binding. K23 deacetylation by SIR2A serves as a molecular switch regulating the nuclease activity of PfAlba3. Co-immunoprecipitation, in vitro deacetylation assay, mass spectrometric analysis of acetylation sites, mutational studies Cell reports Medium 36947546
2025 SIR2A mediates the coupling of NAD+ levels to rDNA silencing. Disruption of NAD+ regeneration during lactate fermentation promotes rDNA de-repression, and SIR2A is identified as the mediator between fluctuating NAD+ levels and rRNA transcriptional outcomes. This links rDNA activation to the metabolic state of the parasite as it transitions from aerobic glycolysis to mitochondrial respiration during host-to-vector transmission. Metabolic perturbation (disruption of NAD+ regeneration), genetic analysis, chromatin/epigenetic assays for rDNA silencing signatures Nature communications Medium 41419483
2025 In P. yoelii, Sir2A physically interacts with GCβ (guanylyl cyclase beta) throughout ookinete development, identified by protein proximity labeling. In mature ookinetes, Sir2A co-localizes with GCβ at the ookinete extrados site (OES) in a mutually dependent manner. Sir2A deacetylates GCβ (which is acetylated in gametocytes) to promote its OES localization. Parasites lacking Sir2A lose GCβ localization at OES, ookinete gliding, and mosquito infection. Elevated NAD+ levels in mature ookinetes drive Sir2A-catalyzed GCβ deacetylation. Protein proximity labeling (BioID), gene knockout, immunofluorescence colocalization, in vivo deacetylation assay, NAD+ quantification, mosquito infection assay Nature communications High 40050296
2024 SIR2A (PfSir2A) exhibits greater enzymatic activity (both deacetylase and de-fatty-acylase) in the presence of DNA for peptide and histone protein substrates. SIR2A demonstrates robust deacetylase activity against nucleosome substrates, stemming from tight binding interactions with the nucleosome. Free fatty acids are endogenous regulators of SIR2A; myristic acid activates deacetylation but inhibits de-fatty-acylation. Synthetic small molecule inhibitors of SIR2A were identified from a sirtuin regulator library. In vitro enzymatic assay with DNA/nucleosome substrates, biochemical binding analysis, fatty acid supplementation assay, compound library screening RSC chemical biology High 39386451 39897407
2022 SIR2A histone deacetylase domain is used as a functional epigenetic repressor in a CRISPRi system (dCas9-Sir2a fusion) to transcriptionally downregulate target genes in P. falciparum without permanent genome changes, demonstrating the sufficiency of the SIR2A deacetylase domain for targeted chromatin silencing. CRISPRi with dCas9-Sir2a fusion, rapamycin-inducible DiCre/loxP system, RT-qPCR for target gene expression Microbiology spectrum Low 35510853

Source papers

Stage 0 corpus · 29 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Telomeric heterochromatin propagation and histone acetylation control mutually exclusive expression of antigenic variation genes in malaria parasites. Cell 401 15820676
2005 Heterochromatin silencing and locus repositioning linked to regulation of virulence genes in Plasmodium falciparum. Cell 393 15820675
2009 Sir2 paralogues cooperate to regulate virulence genes and antigenic variation in Plasmodium falciparum. PLoS biology 199 19402747
2011 Expression of P. falciparum var genes involves exchange of the histone variant H2A.Z at the promoter. PLoS pathogens 87 21379342
2007 Plasmodium falciparum Sir2: an unusual sirtuin with dual histone deacetylase and ADP-ribosyltransferase activity. Eukaryotic cell 81 17827348
2008 Differential association of Orc1 and Sir2 proteins to telomeric domains in Plasmodium falciparum. Journal of cell science 64 18525026
2011 Identification and molecular characterization of an Alba-family protein from human malaria parasite Plasmodium falciparum. Nucleic acids research 60 22006844
2011 Plasmodium falciparum Sir2A preferentially hydrolyzes medium and long chain fatty acyl lysine. ACS chemical biology 57 21992006
2013 Sir2a regulates rDNA transcription and multiplication rate in the human malaria parasite Plasmodium falciparum. Nature communications 55 23443558
2008 Identification of a novel post-translational modification in Plasmodium falciparum: protein sumoylation in different cellular compartments. Cellular microbiology 49 18547337
2008 Nicotinamide inhibits Plasmodium falciparum Sir2 activity in vitro and parasite growth. FEMS microbiology letters 48 18397290
2008 Plasmodium falciparum Sir2 is an NAD+-dependent deacetylase and an acetyllysine-dependent and acetyllysine-independent NAD+ glycohydrolase. Biochemistry 41 18729382
2007 Biochemical characterization of Plasmodium falciparum Sir2, a NAD+-dependent deacetylase. Molecular and biochemical parasitology 37 18221799
2015 Functional analysis of sirtuin genes in multiple Plasmodium falciparum strains. PloS one 34 25780929
2012 The role of N-terminus of Plasmodium falciparum ORC1 in telomeric localization and var gene silencing. Nucleic acids research 30 22379140
2010 Reversible binding of zinc in Plasmodium falciparum Sir2: structure and activity of the apoenzyme. Biochimica et biophysica acta 24 20601220
2009 The effect of Plasmodium falciparum Sir2a histone deacetylase on clonal and longitudinal variation in expression of the var family of virulence genes. International journal for parasitology 23 19666023
2022 A Leak-Free Inducible CRISPRi/a System for Gene Functional Studies in Plasmodium falciparum. Microbiology spectrum 14 35510853
2023 Nuclease activity of Plasmodium falciparum Alba family protein PfAlba3. Cell reports 10 36947546
2021 Febrile temperature causes transcriptional downregulation of Plasmodium falciparum Sirtuins through Hsp90-dependent epigenetic modification. Molecular microbiology 10 33538363
2022 Heat Shock Protein 90 Regulates the Activity of Histone Deacetylase Sir2 in Plasmodium falciparum. mSphere 6 36121150
2019 Differential expression of var subgroups and PfSir2a genes in afebrile Plasmodium falciparum malaria: a matched case-control study. Malaria journal 5 31547813
2024 Plasmodium falciparum gametocyte production correlates with genetic markers of parasite replication but is not influenced by experimental exposure to mosquito biting. EBioMedicine 3 38901148
2023 Molecular characterization and in silico evaluation of surfactins produced by endophytic bacteria from Phanera splendens. Frontiers in chemistry 2 37608862
2022 Alteration of the expression of sirtuins and var genes by heat shock in the malaria parasite Plasmodium falciparum. Molecular and biochemical parasitology 2 35031386
2025 Elevated NAD+ drives Sir2A-mediated GCβ deacetylation and OES localization for Plasmodium ookinete gliding and mosquito infection. Nature communications 1 40050296
2025 A metabolism-chromatin axis promotes differential ribosomal RNA transcription in the human malaria parasite. Nature communications 1 41419483
2025 Biochemical characterization and discovery of inhibitors for PfSir2A: new tricks for an old enzyme. RSC chemical biology 0 39897407
2024 Biochemical Characterization and Inhibitor Discovery for Pf Sir2A - New Tricks for An Old Enzyme. bioRxiv : the preprint server for biology 0 39386451