FP2A

PF3D7_1115700 · cysteine proteinase falcipain 2a

Annotated: 2026-09-08

29 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FP2A (PF3D7_1115700) is the principal trophozoite-stage cysteine protease of Plasmodium falciparum, accounting for at least 93% of soluble trophozoite cysteine protease activity and functioning as the major hemoglobinase during intraerythrocytic development (PMID:10887194). Genetic disruption produces trophozoites with swollen, hemoglobin-filled food vacuoles and heightened sensitivity to both cysteine and aspartic protease inhibitors, establishing FP2A's central and cooperative role in hemoglobin catabolism (PMID:15070727, PMID:16890302). Catalysis depends on an active-site triad (C42, H174, N204), while hemoglobin engagement is directed by a unique C-terminal beta-hairpin exo-site (FP2(arm)) that binds hemoglobin independently of the active site—deletion abolishes hemoglobinase activity without affecting peptide substrate cleavage (PMID:15964982, PMID:15369788); a second structural element, FP2(nose), is required for folding (PMID:16864794). The enzyme cleaves hemoglobin at multiple sites with a strong preference for leucine at P2 (PMID:19357776). FP2A is synthesized as a membrane-bound zymogen that folds without its prodomain (which instead acts as a potent reversible inhibitor) and undergoes autocatalytic processing governed by defined prodomain–mature-domain salt bridges and hydrophobic contacts before delivery to the food vacuole (PMID:11827964, PMID:23077573); trafficking proceeds through a vesicular secretory route directed by a bipartite prodomain motif and requires interaction with PTEX components (PMID:17698213, PMID:17565983, PMID:37523385). Within the food vacuole FP2A assembles into an ~200-kDa complex with heme detoxification protein and plasmepsins that couples hemoglobin degradation to hemozoin formation (PMID:23471987). FP2A activity is constrained by the endogenous inhibitors falstatin and ICP and is allosterically inhibited by heme (PMID:17083274, PMID:21742259, PMID:25791019). Reduced FP2A enzymatic activity, associated with naturally occurring Southeast Asian polymorphisms, is linked to decreased artemisinin sensitivity (PMID:29659945).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps

2000 High
Established that FP2A is the dominant trophozoite cysteine protease and a hemoglobinase, defining its core biological role in the intraerythrocytic parasite.

Evidence Native enzyme purification plus recombinant refolding, activity assays against hemoglobin/globin, and immunolocalization in P. falciparum

PMID:10887194
Open questions at the time
- Relative contribution versus other food-vacuole proteases not resolved by biochemistry alone
- In vivo essentiality not addressed at this stage
2002 High
Resolved the folding logic of the enzyme by showing the prodomain is not a folding chaperone but a high-affinity reversible inhibitor, while an N-terminal mature-domain segment enables folding.

Evidence Recombinant pro/mature constructs, in trans peptide complementation, and Ki determination in E. coli-expressed protein

PMID:11827964
Open questions at the time
- Physiological timing of prodomain release in vivo not defined
- How inhibition is relieved during activation unclear
2004 High
Genetic disruption confirmed FP2A's specific in-parasite role in hemoglobin degradation and revealed cooperative action with aspartic proteases.

Evidence Gene knockout by homologous recombination with morphology, activity, and inhibitor sensitivity assays; catalytic triad defined by mutagenesis

PMID:15070727 PMID:15369788
Open questions at the time
- Residual hemoglobin digestion in KO indicates redundancy whose molecular basis is unspecified
- Non-hemoglobin roles not tested
2005 High
Identified the FP2(arm) exo-site as the determinant of hemoglobinase activity, separating hemoglobin capture from the catalytic active site, and mapped trafficking and processing to a pre-food-vacuole compartment.

Evidence Deletion mutagenesis with substrate/binding assays; metabolic labeling, immunoEM, fractionation, and inhibitor panel in P. falciparum

PMID:15664655 PMID:15964982
Open questions at the time
- Structural basis of exo-site hemoglobin recognition not yet visualized
- Identity of the processing compartment not molecularly defined
2006 High
Structural determination of mature FP2A and its cystatin complex revealed the FP2(arm) and FP2(nose) motifs and demonstrated pH-dependent hemoglobin binding and trans-processing, providing an atomic framework for substrate capture and folding.

Evidence X-ray crystallography (3.1 Å free, 2.9 Å cystatin complex) with mutagenesis and pH-dependent binding assays; independent KO replication in 3D7

PMID:16777845 PMID:16864794 PMID:16890302
Open questions at the time
- Structure of an FP2A–hemoglobin complex still lacking
- Dynamics linking pH to exo-site engagement inferred, not directly captured
2006 Medium
Identified falstatin as an endogenous inhibitor of FP2A and linked its regulation to merozoite invasion, extending FP2A's relevance beyond food-vacuole hemoglobin digestion.

Evidence Recombinant falstatin inhibition assays and antibody-blocking erythrocyte invasion assays

PMID:17083274
Open questions at the time
- Direct in-parasite demonstration of FP2A action during invasion not shown
- Single-lab functional linkage
2007 Medium
Defined the secretory trafficking route and a bipartite prodomain trafficking signal directing FP2A to the food vacuole.

Evidence GFP chimeras, serial truncation/point mutants, FRAP, and confocal imaging in transgenic P. falciparum

PMID:17565983 PMID:17698213
Open questions at the time
- Trafficking receptors recognizing the bipartite motif unidentified
- Single-lab GFP-fusion evidence
2009 High
Mapped substrate specificity (P2 leucine preference, distributed hemoglobin cleavage) and the active-site plasticity distinguishing FP2A from falcipain-3, informing inhibitor design.

Evidence Positional-scanning libraries, 18O-labeling cleavage mapping, MS-based hemoglobin digestion, and E-64 co-crystal structure

PMID:19128015 PMID:19357776
Open questions at the time
- Physiological ordering of hemoglobin cleavage in vivo not established
- Contribution of exo-site to cleavage-site selection not deconvolved
2011 High
Extended the inhibitor repertoire by resolving an ICP (chagasin-like) inhibitor bound to FP2A, revealing a distinct binding mode.

Evidence X-ray crystallography of PbICP-C:FP2A complex at 2.6 Å

PMID:21742259
Open questions at the time
- Physiological role of ICP–FP2A regulation in vivo not addressed
- Inhibitor is a P. berghei protein bound to P. falciparum FP2A
2012 Medium
Defined the molecular determinants of autoactivation, showing specific salt bridges and hydrophobic prodomain–mature-domain contacts are required for autoprocessing.

Evidence Mutagenesis, circular dichroism, and trans-activation assays on recombinant FP2A

PMID:23077573
Open questions at the time
- In vivo requirement of these residues not tested
- Single-lab in vitro system
2013 High
Placed FP2A within an ~200-kDa food-vacuole complex coupling hemoglobin degradation to hemozoin formation, integrating proteolysis with heme detoxification.

Evidence Co-IP/MS, gel filtration, glycerol gradient co-sedimentation, and in vitro hemoglobin-to-hemozoin reconstitution

PMID:23471987
Open questions at the time
- Stoichiometry and spatial organization of the complex undefined
- Whether complex assembly is required for activity in vivo unclear
2015 Medium
Identified heme as an allosteric inhibitor of FP2A via an inducible binding site, suggesting product feedback regulation of hemoglobin digestion.

Evidence Enzyme kinetics, porphyrin analogue SAR, and docking/molecular dynamics

PMID:25791019
Open questions at the time
- Binding site identified computationally, not crystallographically
- Physiological significance of the feedback not demonstrated in parasites
2018 Medium
Linked reduced FP2A enzymatic activity from natural polymorphisms to increased ring-stage survival, connecting FP2A function to artemisinin sensitivity.

Evidence Full-length sequencing of 140 isolates, haplotype-based activity assays, and ring-stage survival assays

PMID:29659945
Open questions at the time
- Mechanistic link between hemoglobin digestion and artemisinin activation not directly demonstrated
- Single-lab functional haplotype analysis
2023 Medium
Revealed a PTEX-dependent step in FP2A trafficking, indicating translocation into the parasitophorous vacuole en route to the food vacuole.

Evidence Conditional PTEX150 knockdown, GFP-fusion lines, Co-IP, and hemoglobin digestion assays

PMID:37523385
Open questions at the time
- Direct mechanism of FP2A passage through PTEX unresolved
- Single-lab conditional knockdown

Open questions

Synthesis pass · forward-looking unresolved questions

The precise coupling between FP2A hemoglobin catabolism, heme handling within the ~200-kDa complex, and artemisinin activation remains mechanistically unresolved.
No structure of FP2A bound to hemoglobin or within the food-vacuole complex
In-parasite necessity of autoactivation residues and heme-feedback site untested
Molecular mechanism of PTEX-mediated FP2A translocation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification

Partners

FALSTATIN (ENDOGENOUS CYSTEINE PROTEASE INHIBITOR) [#12]HEME DETOXIFICATION PROTEIN (HDP) [#13]ICP / PBICP-C (CHAGASIN-LIKE INHIBITOR) [#15]PTEX COMPONENTS INCLUDING PTEX150 [#20]

Complex memberships

FP2A:PbICP-C (chagasin-like inhibitor) complex [#15]FP2A:cystatin complex [#5]FP2A:falstatin inhibitory complex [#12]~200-kDa food-vacuole hemoglobin-degradation complex containing FP2A, heme detoxification protein, and plasmepsins [#13]

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus

Year	Finding	Method	Journal	Conf	PMIDs
2000	FP2A (falcipain-2) is the principal trophozoite cysteine protease of P. falciparum, responsible for at least 93% of trophozoite soluble cysteine protease activity; it is concentrated in food vacuoles, hydrolyzes both native hemoglobin and denatured globin optimally at acid pH in a reducing environment, and can initiate cleavage of native hemoglobin.	Affinity chromatography purification of native enzyme; recombinant expression in E. coli with refolding; enzymatic assays against peptide substrates, native hemoglobin, and denatured globin; immunolocalization	The Journal of biological chemistry	High	10887194
2004	Genetic disruption of the FP2A gene in P. falciparum causes markedly diminished trophozoite cysteine protease activity and swollen, hemoglobin-filled food vacuoles, confirming FP2A's specific role in hemoglobin hydrolysis during the trophozoite stage; knockout parasites showed increased sensitivity to cysteine and aspartic protease inhibitors, revealing cooperative action between cysteine and aspartic proteases in hemoglobin degradation.	Gene disruption (knockout) by homologous recombination; morphological analysis; cysteine protease activity assay; drug sensitivity assays (E-64, leupeptin, pepstatin)	Proceedings of the National Academy of Sciences of the United States of America	High	15070727
2006	Disruption of the FP2A gene in the 3D7 strain produced swollen hemoglobin-filled food vacuoles in trophozoites; FP2A knockout parasites were twice as sensitive to cysteine protease inhibitors and over 1000-fold more sensitive to an aspartic protease inhibitor compared to wild-type, further supporting FP2A's role in hemoglobin hydrolysis and the cooperative interplay between cysteine and aspartic proteases.	Gene disruption in 3D7 strain; morphological analysis; drug sensitivity assays	Molecular and biochemical parasitology	High	16890302
2005	FP2A possesses a unique 14-amino acid C-terminal beta-hairpin motif (FP2(arm)) that mediates binding to hemoglobin independent of the active site; deletion of 10 residues of this motif abolishes activity against hemoglobin and globin but not against peptide substrates, casein, or gelatin. This motif also mediates interaction with the prodomain inhibitor of FP2A.	Site-directed mutagenesis (deletion mutant Delta10FP2A); enzymatic assays against peptide substrates, hemoglobin, globin, casein, gelatin; E-64-inhibited complex pulldown to assess hemoglobin binding; peptide competition assay	Proceedings of the National Academy of Sciences of the United States of America	High	15964982
2006	Crystal structure of mature FP2A at 3.1 Å resolution reveals a dynamic beta-hairpin hemoglobin-binding motif (FP2(arm)), a flexible N-terminal alpha-helical extension, and a unique active-site cleft. Biochemical assays showed that mature FP2A can proteolytically process its own precursor in trans at neutral to weakly alkaline pH, that hemoglobin binding is strictly pH-dependent, and that FP2A preferentially binds methemoglobin over hemoglobin.	X-ray crystallography (3.1 Å); biochemical processing assays; hemoglobin-binding assays under varying pH conditions	The Journal of biological chemistry	High	16777845
2006	Crystal structure of FP2A in complex with the protease inhibitor cystatin at 2.9 Å reveals two unique structural motifs: FP2(nose), a short N-terminal segment required for folding without a prodomain, and FP2(arm), required for hemoglobinase activity. Mutagenesis of two Tyr within FP2(nose) and a conserved Glu outside it confirmed their functional roles in folding. FP2(arm) bears a negative charge cluster suggesting an exo-site for hemoglobin binding.	X-ray crystallography (crystal structure with cystatin); site-directed mutagenesis; functional activity assays	Proceedings of the National Academy of Sciences of the United States of America	High	16864794
2009	Crystal structure of FP2A at 2.9 Å bound to the covalent inhibitor E-64 reveals that relative shape and flexibility of the S2 pocket are influenced by discrete amino acid substitutions, explaining kinetic differences between FP2A and falcipain-3. This represents the first crystal structure of a plasmodial cysteine protease with a small molecule inhibitor.	X-ray crystallography (2.9 Å, FP2A-E64 complex); structural comparison with falcipain-3-leupeptin complex	Journal of medicinal chemistry	High	19128015
2002	FP2A folding does not require its prodomain; instead, a 17-amino acid N-terminal segment of the mature protease acts as a chaperone-like peptide required for correct folding. The prodomain functions as a potent, competitive, and reversible inhibitor of mature FP2A (Ki ~10^-10 M) rather than as a folding chaperone.	Recombinant expression of multiple pro- and mature domain constructs in E. coli; refolding assays; in trans complementation with isolated peptide; kinetic inhibition assays (Ki determination)	The Journal of biological chemistry	High	11827964
2005	FP2A is synthesized through the trophozoite stage, is localized to the food vacuole (confirmed by immunofluorescence and immunoelectron microscopy), is synthesized as a membrane-bound proform that is processed to a soluble mature form more quickly than falcipain-3, and its autocatalytic processing occurs in a specific cellular compartment before delivery to the food vacuole (lipophilic but not hydrophilic cysteine protease inhibitors block processing, while both block hemoglobinase activity).	Metabolic labeling and immunoprecipitation; immunofluorescence microscopy; immunoelectron microscopy; subcellular fractionation; inhibitor studies with E-64, E-64d, leupeptin, brefeldin A	Molecular and biochemical parasitology	High	15664655
2007	FP2A is trafficked to the food vacuole via a classical vesicle-mediated secretory pathway involving the endoplasmic reticulum and Golgi-like apparatus, carried in cytostomal vesicles; the N-terminal sequence (residues 1–120) is sufficient for food vacuole targeting.	Transgenic parasites expressing falcipain-2-GFP chimeras; FRAP (photobleaching); confocal microscopy; anti-falcipain-2 antibody immunolocalization	Molecular and biochemical parasitology	Medium	17698213
2007	FP2A requires a bipartite motif in its prodomain for food vacuole trafficking: both a 20-amino acid stretch of the lumenal portion and a 10-amino acid stretch of the cytoplasmic portion are required for efficient trafficking; mutants with altered trafficking are arrested at the plasma membrane.	GFP chimeras with serial truncations, deletions, and point mutations in transgenic P. falciparum; fluorescence microscopy	The Journal of biological chemistry	Medium	17565983
2001	Recombinant FP2A cleaves erythrocyte membrane skeletal proteins ankyrin and protein 4.1 in vitro.	In vitro cleavage assay with recombinant FP2A against purified erythrocyte membrane proteins	Molecular and biochemical parasitology	Medium	11463472
2006	FP2A is a target of falstatin, an endogenous P. falciparum cysteine protease inhibitor; recombinant falstatin potently and reversibly inhibits FP2A activity, and antibodies blocking falstatin's inhibitory activity against native and recombinant FP2A dose-dependently decreased erythrocyte invasion by merozoites.	Recombinant expression of falstatin in E. coli; enzyme inhibition assays against FP2A; antibody blocking assays; erythrocyte invasion assays	PLoS pathogens	Medium	17083274
2013	FP2A is a component of an ~200-kDa protein complex in the food vacuole required for hemoglobin degradation and hemozoin formation; in vitro, FP2A and heme detoxification protein associate with each other to efficiently convert hemoglobin to hemozoin.	Co-immunoprecipitation followed by mass spectrometry; gel filtration co-elution; glycerol gradient co-sedimentation; in vitro protein interaction assays; in vitro hemoglobin-to-hemozoin conversion assay	Proceedings of the National Academy of Sciences of the United States of America	High	23471987
2009	FP2A shows strong substrate preference for leucine at the P2 position when cleaving peptide substrates, and cleaves hemoglobin at multiple sites across alpha and beta globin chains without a highly ordered pattern, indicating a principal but non-sequential role in hemoglobin hydrolysis.	Random P1–P4 amino acid substrate libraries (positional scanning); overlapping peptide hydrolysis with proteolysis-dependent 18O labeling; intact hemoglobin digestion with product identification by MS	PloS one	High	19357776
2011	The C-terminal inhibitory domain of P. berghei ICP (PbICP-C) forms a 1:1 complex with FP2A, establishing FP2A as a target of ICP-class inhibitors (I42/chagasin-like family); the crystal structure at 2.6 Å reveals that ICP uses a distinct binding mode compared to other chagasin-like inhibitors.	X-ray crystallography (2.6 Å, PbICP-C:FP2A complex)	Structure (London, England : 1993)	High	21742259
2012	Auto-activation of FP2A requires specific salt bridges (Arg185–Glu221 and Glu210–Lys403) and hydrophobic interactions (Phe214, Trp449, Trp453) between its prodomain and mature domain; mutagenesis of these residues abolishes autoprocessing.	Recombinant expression of wild-type and mutant FP2A in E. coli; circular dichroism; trans-activation assays; mutagenesis of salt bridge and hydrophobic residues	PloS one	Medium	23077573
2015	Heme binds to FP2A with 1:1 stoichiometry and inhibits FP2A activity against both hemoglobin and peptide substrates through a noncompetitive-like mechanism (substrate inhibition induced by heme); a novel inducible heme-binding site adjacent to the catalytic site was identified by docking and molecular dynamics; inhibition requires both propionic and vinyl groups of the heme porphyrin, with minor contribution from iron.	Enzyme kinetic assays; porphyrin analogue structure-activity relationship screen; docking and molecular dynamics simulation	Archives of biochemistry and biophysics	Medium	25791019
2004	Site-directed mutagenesis of FP2A identified active-site catalytic triad residues C42, H174, and N204 as essential for catalysis; substitutions at C99 and C119 caused structural alterations with >97% reduction in enzyme activity; S149 is required for specific peptide substrate interactions.	Site-directed mutagenesis (nine mutants); recombinant expression in E. coli; affinity purification; enzymatic activity assays	Biochemical and biophysical research communications	Medium	15369788
2018	FP2A (PF3D7_1115700) is required for potent artemisinin activity; haplotypes bearing naturally occurring FP2A polymorphisms from Southeast Asia showed increased ring survival and significantly reduced FP2A enzymatic activity compared to wild-type, with haplotype group I showing the slowest protease kinetics and reduced parasite fitness.	Full-length gene sequencing of 140 P. falciparum isolates; functional haplotype analysis; enzymatic activity assays; ring-stage survival assays	The Journal of infectious diseases	Medium	29659945
2023	FP2A interacts with PTEX core components (including PTEX150) and this interaction is required for efficient trafficking of FP2A to the food vacuole; PTEX150 knockdown substantially perturbs hemoglobin digestion, suggesting FP2A is translocated into the parasitophorous vacuole via PTEX to reach the cytostome prior to food vacuole entry.	Conditional knockdown of PTEX150; transgenic parasite lines with GFP fusions; co-immunoprecipitation; hemoglobin digestion assays	PLoS pathogens	Medium	37523385
2019	Crystal structure of FP2A at 3.45 Å in complex with an (E)-chalcone small-molecule inhibitor reveals that the inhibitor binds to the rear of the substrate-binding cleft, identifying a novel small-molecule binding site distinct from the active site.	X-ray crystallography (3.45 Å, FP2A-(E)-chalcone complex); structural comparison with previous FP2A complexes	Malaria journal	Medium	31791339
2021	Crystal structure of FP2A from the drug-resistant P. falciparum 3D7 strain (with variants R12K, E14N, P100T, G102D in the mature domain) resolved at 3.5 Å (E-64 complex) and 3.4 Å (iodoacetamide complex) reveals two solvent-exposed pockets including one structurally homologous to the allosteric binding site of human cathepsin K, and shows strain-specific multiple binding modes for E-64.	X-ray crystallography (3.5 Å and 3.4 Å with two inhibitors); structural analysis; docking and normal mode analysis	Biochemical and biophysical research communications	Medium	34974303

Source papers

Stage 0 corpus · 29 papers · ranked by NIH iCite citations

Year	Title	Journal	Citations	PMID
2000	Characterization of native and recombinant falcipain-2, a principal trophozoite cysteine protease and essential hemoglobinase of Plasmodium falciparum.	The Journal of biological chemistry	292	10887194
2004	Gene disruption confirms a critical role for the cysteine protease falcipain-2 in hemoglobin hydrolysis by Plasmodium falciparum.	Proceedings of the National Academy of Sciences of the United States of America	245	15070727
2013	Protein complex directs hemoglobin-to-hemozoin formation in Plasmodium falciparum.	Proceedings of the National Academy of Sciences of the United States of America	131	23471987
2009	Structures of falcipain-2 and falcipain-3 bound to small molecule inhibitors: implications for substrate specificity.	Journal of medicinal chemistry	127	19128015
2006	Gene disruptions demonstrate independent roles for the four falcipain cysteine proteases of Plasmodium falciparum.	Molecular and biochemical parasitology	125	16890302
2005	The Plasmodium falciparum cysteine protease falcipain-2 captures its substrate, hemoglobin, via a unique motif.	Proceedings of the National Academy of Sciences of the United States of America	113	15964982
2014	Polymorphisms in K13 and falcipain-2 associated with artemisinin resistance are not prevalent in Plasmodium falciparum isolated from Ugandan children.	PloS one	103	25144768
2006	Structural and functional characterization of Falcipain-2, a hemoglobinase from the malarial parasite Plasmodium falciparum.	The Journal of biological chemistry	102	16777845
2006	Structural basis for unique mechanisms of folding and hemoglobin binding by a malarial protease.	Proceedings of the National Academy of Sciences of the United States of America	86	16864794
2001	Recombinant falcipain-2 cleaves erythrocyte membrane ankyrin and protein 4.1.	Molecular and biochemical parasitology	75	11463472
2006	Falstatin, a cysteine protease inhibitor of Plasmodium falciparum, facilitates erythrocyte invasion.	PLoS pathogens	72	17083274
2005	Biosynthesis, localization, and processing of falcipain cysteine proteases of Plasmodium falciparum.	Molecular and biochemical parasitology	67	15664655
2006	Novel peptidomimetic cysteine protease inhibitors as potential antimalarial agents.	Journal of medicinal chemistry	57	16722625
2009	Hemoglobin cleavage site-specificity of the Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3.	PloS one	55	19357776
2002	Folding of the Plasmodium falciparum cysteine protease falcipain-2 is mediated by a chaperone-like peptide and not the prodomain.	The Journal of biological chemistry	50	11827964
2007	Falcipain cysteine proteases require bipartite motifs for trafficking to the Plasmodium falciparum food vacuole.	The Journal of biological chemistry	40	17565983
2011	Structural basis for the regulation of cysteine-protease activity by a new class of protease inhibitors in Plasmodium.	Structure (London, England : 1993)	31	21742259
2018	Plasmodium falciparum Falcipain-2a Polymorphisms in Southeast Asia and Their Association With Artemisinin Resistance.	The Journal of infectious diseases	30	29659945
2007	Food vacuole targeting and trafficking of falcipain-2, an important cysteine protease of human malaria parasite Plasmodium falciparum.	Molecular and biochemical parasitology	24	17698213
2019	The complex of Plasmodium falciparum falcipain-2 protease with an (E)-chalcone-based inhibitor highlights a novel, small, molecule-binding site.	Malaria journal	22	31791339
2012	The Ionic and hydrophobic interactions are required for the auto activation of cysteine proteases of Plasmodium falciparum.	PloS one	15	23077573
2004	Homology modeling and mutagenesis analyses of Plasmodium falciparum falcipain 2A: implications for rational drug design.	Biochemical and biophysical research communications	15	15369788
2015	Allosteric regulation of the Plasmodium falciparum cysteine protease falcipain-2 by heme.	Archives of biochemistry and biophysics	12	25791019
2005	Characterization of amino acid variation at strategic positions in parasite and human proteases for selective inhibition of falcipains in Plasmodium falciparum.	Biochemical and biophysical research communications	10	16095562
2019	Inhibition of Plasmodium falciparum cysteine protease falcipain-2 by a human cross-class inhibitor serpinB3: A mechanistic insight.	Biochimica et biophysica acta. Proteins and proteomics	8	31247344
2023	PTEX helps efficiently traffic haemoglobinases to the food vacuole in Plasmodium falciparum.	PLoS pathogens	7	37523385
2021	New insights of falcipain 2 structure from Plasmodium falciparum 3D7 strain.	Biochemical and biophysical research communications	5	34974303
2014	Dynamical footprint of falcipain-2 catalytic triad in hemoglobin-β-bound state.	Journal of biomolecular structure & dynamics	4	24943200
2025	Decoding substrate recognition in malapain-2 through structural and mutational insights.	Computational and structural biotechnology journal	0	41245893