SUMF1 Human, Sf9
Description
Functional Role in Sulfatase Activation
SUMF1 acts as a formylglycine-generating enzyme (FGE), enabling sulfatases to hydrolyze sulfate esters in substrates like glycosaminoglycans and sulfolipids . Mutations in SUMF1 cause multiple sulfatase deficiency (MSD), a lysosomal storage disorder characterized by impaired degradation of sulfated metabolites .
Key Mechanism:
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Oxygen-dependent catalysis: SUMF1 requires molecular oxygen (O₂) to oxidize cysteine to FGly, consuming 1 mole of O₂ per reaction .
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Reductant dependency: Activity is sustained by thiol-based reductants (e.g., DTT) to maintain reduced cysteine residues (Cys336/Cys341) in its catalytic site .
Gene Therapy Enhancement
Co-delivery of SUMF1 with sulfatase genes via viral vectors (AAV or lentivirus) significantly boosts sulfatase activity in deficient cells:
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In MPSIIIA mice, intramuscular co-injection of SUMF1 and sulfamidase (SGSH) increased enzyme activity by 2-fold compared to sulfamidase alone, improving clearance of glycosaminoglycan storage .
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Similar enhancements were observed in fibroblasts from patients with metachromatic leukodystrophy (MLD) and chondrodysplasia punctata (CDPX) .
Disease Modeling
SUMF1 Human, Sf9 is used to:
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Study MSD pathogenesis linked to SUMF1 mutations (e.g., C336R abolishes enzyme activity) .
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Develop enzyme replacement therapies by optimizing sulfatase activation thresholds .
Comparative Analysis: Sf9 vs. E. coli-Produced SUMF1
Research Findings
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In vitro: Co-expression of SUMF1 with sulfatases in COS-7 cells increased enzymatic activity by up to 8-fold .
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In vivo: AAV-mediated delivery of SUMF1 and SGSH in MPSIIIA mice reduced lysosomal storage pathology by 50% compared to SGSH alone .
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Structural Insight: The C-terminal His tag does not interfere with SUMF1’s interaction with sulfatase substrates .
Product Specs
SUMF1, AAPA3037, FGE, UNQ3037, Formylglycine-generating enzyme, C-alpha-formylglycine-generating enzyme 1, Sulfatase-modifying factor 1.
Sf9, Insect cells.
SQEAGTGAGA GSLAGSCGCG TPQRPGAHGS SAAAHRYSRE ANAPGPVPGE RQLAHSKMVP IPAGVFTMGT DDPQIKQDGE APARRVTIDA FYMDAYEVSN TEFEKFVNST GYLTEAEKFG DSFVFEGMLS EQVKTNIQQA VAAAPWWLPV KGANWRHPEG PDSTILHRPD HPVLHVSWND AVAYCTWAGK RLPTEAEWEY SCRGGLHNRL FPWGNKLQPK GQHYANIWQG EFPVTNTGED GFQGTAPVDA FPPNGYGLYN IVGNAWEWTS DWWTVHHSVE ETLNPKGPPS GKDRVKKGGS YMCHRSYCYR YRCAARSQNT PDSSASNLGF RCAADRLPTM DHHHHHH.
Product Science Overview
The SUMF1 gene is located on chromosome 3p26.1 in humans . The gene encodes a protein that is part of the SUMF protein family. The primary function of SUMF1 is to catalyze the hydrolysis of sulfate esters by oxidizing a cysteine residue in the substrate sulfatase to an active site 3-oxoalanine residue, also known as C-alpha-formylglycine .
SUMF1 is essential for the activation of sulfatases, which are enzymes that catalyze the hydrolysis of sulfate esters such as glycosaminoglycans, sulfolipids, and steroid sulfates . The catalytic residue in the active site of eukaryotic sulfatases, C-alpha-formylglycine (FGly), is post-translationally generated from a cysteine by SUMF1 in the endoplasmic reticulum (ER) . This modification is critical for the proper functioning of sulfatases.
Mutations in the SUMF1 gene can lead to multiple sulfatase deficiency (MSD), a lysosomal storage disorder . This condition results from the inability to form the FGly residue, leading to inactive sulfatases and the accumulation of sulfated substrates in lysosomes . MSD is characterized by a range of symptoms, including developmental delays, skeletal abnormalities, and neurological deficits .
Recombinant SUMF1 produced in Sf9 cells (a cell line derived from the fall armyworm, Spodoptera frugiperda) is used for research and therapeutic purposes . The recombinant form retains the enzymatic activity necessary for the post-translational modification of sulfatases, making it a valuable tool for studying the function and regulation of these enzymes .
