SPT_SPHPI
ID SPT_SPHPI Reviewed; 420 AA.
AC Q93UV0;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Serine palmitoyltransferase {ECO:0000303|PubMed:11279212};
DE Short=SPT {ECO:0000303|PubMed:11279212};
DE EC=2.3.1.50 {ECO:0000269|PubMed:11279212, ECO:0000269|PubMed:17557831, ECO:0000269|PubMed:17559874, ECO:0000269|PubMed:19376777};
GN Name=spt {ECO:0000303|PubMed:17559874};
GN Synonyms=SPT1 {ECO:0000303|PubMed:11279212};
GN ORFNames=HKX06_04505 {ECO:0000312|EMBL:NNG56642.1},
GN I6G38_17245 {ECO:0000312|EMBL:QPT08440.1};
OS Sphingomonas paucimobilis (Pseudomonas paucimobilis).
OC Bacteria; Proteobacteria; Alphaproteobacteria; Sphingomonadales;
OC Sphingomonadaceae; Sphingomonas.
OX NCBI_TaxID=13689;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-6, FUNCTION,
RP CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND SUBUNIT.
RC STRAIN=EY2395;
RX PubMed=11279212; DOI=10.1074/jbc.m101550200;
RA Ikushiro H., Hayashi H., Kagamiyama H.;
RT "A water-soluble homodimeric serine palmitoyltransferase from Sphingomonas
RT paucimobilis EY2395T strain. Purification, characterization, cloning, and
RT overproduction.";
RL J. Biol. Chem. 276:18249-18256(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FKI-L5-BR-P1;
RA Bijlani S., Singh N.K., Mason C.E., Wang C.C., Venkateswaran K.;
RT "Draft Genome Sequences of Sphingomonas sp. Isolated from the International
RT Space Station.";
RL Submitted (MAY-2020) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 10829 / DSM 30198 / FDAARGOS_881;
RA Sproer C., Gronow S., Severitt S., Schroder I., Tallon L., Sadzewicz L.,
RA Zhao X., Boylan J., Ott S., Bowen H., Vavikolanu K., Mehta A.,
RA Aluvathingal J., Nadendla S., Lowell S., Myers T., Yan Y., Sichtig H.;
RT "FDA dAtabase for Regulatory Grade micrObial Sequences (FDA-ARGOS):
RT Supporting development and validation of Infectious Disease Dx tests.";
RL Submitted (DEC-2020) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBCELLULAR LOCATION.
RC STRAIN=ATCC 27052;
RX PubMed=17557831; DOI=10.1128/jb.00194-07;
RA Ikushiro H., Islam M.M., Tojo H., Hayashi H.;
RT "Molecular characterization of membrane-associated soluble serine
RT palmitoyltransferases from Sphingobacterium multivorum and Bdellovibrio
RT stolpii.";
RL J. Bacteriol. 189:5749-5761(2007).
RN [5] {ECO:0007744|PDB:2JG2, ECO:0007744|PDB:2JGT}
RP X-RAY CRYSTALLOGRAPHY (1.30 ANGSTROMS) IN COMPLEX WITH PYRIDOXAL PHOSPHATE,
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND SUBUNIT.
RC STRAIN=13361;
RX PubMed=17559874; DOI=10.1016/j.jmb.2007.04.086;
RA Yard B.A., Carter L.G., Johnson K.A., Overton I.M., Dorward M., Liu H.,
RA McMahon S.A., Oke M., Puech D., Barton G.J., Naismith J.H.,
RA Campopiano D.J.;
RT "The structure of serine palmitoyltransferase; gateway to sphingolipid
RT biosynthesis.";
RL J. Mol. Biol. 370:870-886(2007).
RN [6] {ECO:0007744|PDB:2W8J, ECO:0007744|PDB:2W8T, ECO:0007744|PDB:2W8U, ECO:0007744|PDB:2W8V, ECO:0007744|PDB:2W8W}
RP X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF 2-420 OF WILD-TYPE AND MUTANTS IN
RP COMPLEXES WITH PYRIDOXAL PHOSPHATE AND PLP-BOUND SERINE, FUNCTION,
RP CATALYTIC ACTIVITY, REACTION MECHANISM, COFACTOR, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBUNIT, AND MUTAGENESIS OF ASN-100 AND ARG-378.
RC STRAIN=EY2395;
RX PubMed=19376777; DOI=10.1074/jbc.m109.008680;
RA Raman M.C.C., Johnson K.A., Yard B.A., Lowther J., Carter L.G.,
RA Naismith J.H., Campopiano D.J.;
RT "The external aldimine form of serine palmitoyltransferase: structural,
RT kinetic, and spectroscopic analysis of the wild-type enzyme and HSAN1
RT mutant mimics.";
RL J. Biol. Chem. 284:17328-17339(2009).
RN [7] {ECO:0007744|PDB:2XBN}
RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 2-420 OF CYCLOSERINE-INACTIVATED
RP SPT, AND ACTIVITY REGULATION.
RX PubMed=20445930; DOI=10.1039/c003743e;
RA Lowther J., Yard B.A., Johnson K.A., Carter L.G., Bhat V.T., Raman M.C.,
RA Clarke D.J., Ramakers B., McMahon S.A., Naismith J.H., Campopiano D.J.;
RT "Inhibition of the PLP-dependent enzyme serine palmitoyltransferase by
RT cycloserine: evidence for a novel decarboxylative mechanism of
RT inactivation.";
RL Mol. Biosyst. 6:1682-1693(2010).
RN [8] {ECO:0007744|PDB:4BMK}
RP X-RAY CRYSTALLOGRAPHY (1.62 ANGSTROMS) OF 2-420 OF MUTANT ALA-265 IN
RP COMPLEX WITH PLP-MYRIOCIN ALDIMINE, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP LYS-265.
RX PubMed=23957439; DOI=10.1021/ja4059876;
RA Wadsworth J.M., Clarke D.J., McMahon S.A., Lowther J.P., Beattie A.E.,
RA Langridge-Smith P.R., Broughton H.B., Dunn T.M., Naismith J.H.,
RA Campopiano D.J.;
RT "The chemical basis of serine palmitoyltransferase inhibition by
RT myriocin.";
RL J. Am. Chem. Soc. 135:14276-14285(2013).
CC -!- FUNCTION: Catalyzes the condensation of L-serine with palmitoyl-CoA
CC (hexadecanoyl-CoA) to produce 3-oxosphinganine (PubMed:11279212,
CC PubMed:17557831, PubMed:17559874, PubMed:19376777). Exhibits a broad
CC substrate specificity concerning the chain length and the degree of
CC unsaturation of acyl-CoA (PubMed:11279212, PubMed:19376777).
CC {ECO:0000269|PubMed:11279212, ECO:0000269|PubMed:17557831,
CC ECO:0000269|PubMed:17559874, ECO:0000269|PubMed:19376777}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hexadecanoyl-CoA + L-serine = 3-oxosphinganine + CO2 +
CC CoA; Xref=Rhea:RHEA:14761, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:33384, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379,
CC ChEBI:CHEBI:58299; EC=2.3.1.50;
CC Evidence={ECO:0000269|PubMed:11279212, ECO:0000269|PubMed:17557831,
CC ECO:0000269|PubMed:17559874, ECO:0000269|PubMed:19376777};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14762;
CC Evidence={ECO:0000269|PubMed:11279212};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:11279212, ECO:0000269|PubMed:17559874,
CC ECO:0000269|PubMed:19376777};
CC -!- ACTIVITY REGULATION: Not inhibited by relatively high concentrations of
CC palmitoyl-CoA (PubMed:11279212). Inhibited by both D-cycloserine (DCS)
CC and L-cycloserine (LCS), which inactivate SPT by transamination to form
CC a free pyridoxamine 5'-phosphate (PMP) and beta-aminooxyacetaldehyde
CC that remain bound at the active site (PubMed:20445930). Inhibition is
CC reversed by incubation with excess pyridoxal phosphate
CC (PubMed:20445930). Inhibited by the fungal natural product myriocin,
CC which acts as a competitive inhibitor for both L-serine and palmitoyl-
CC CoA substrates (PubMed:23957439). {ECO:0000269|PubMed:11279212,
CC ECO:0000269|PubMed:20445930, ECO:0000269|PubMed:23957439}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.23 mM for L-serine {ECO:0000269|PubMed:11279212};
CC KM=4.7 mM for L-serine {ECO:0000269|PubMed:17557831};
CC KM=1.4 mM for L-serine {ECO:0000269|PubMed:19376777};
CC KM=0.87 mM for palmitoyl-CoA {ECO:0000269|PubMed:11279212};
CC KM=0.69 mM for palmitoyl-CoA {ECO:0000269|PubMed:17557831};
CC KM=35.4 uM for palmitoyl-CoA {ECO:0000269|PubMed:19376777};
CC KM=2324.9 uM for decanoyl-CoA {ECO:0000269|PubMed:19376777};
CC KM=822.2 uM for lauroyl-CoA {ECO:0000269|PubMed:19376777};
CC KM=97.1 uM for myristoyl-CoA {ECO:0000269|PubMed:19376777};
CC KM=13.7 uM for stearoyl-CoA {ECO:0000269|PubMed:19376777};
CC Note=kcat is 140 min(-1) with palmitoyl-CoA as substrate
CC (PubMed:11279212). kcat is 2.3 sec(-1) with palmitoyl-CoA as
CC substrate (PubMed:17557831). kcat is 1.150 sec(-1) with palmitoyl-CoA
CC as substrate (PubMed:19376777). kcat is 0.045 sec(-1) with decanoyl-
CC CoA as substrate (PubMed:19376777). kcat is 0.262 sec(-1) with
CC lauroyl-CoA as substrate (PubMed:19376777). kcat is 0.601 sec(-1)
CC with myristoyl-CoA as substrate (PubMed:19376777). kcat is 0.898
CC sec(-1) with stearoyl-CoA as substrate (PubMed:19376777). kcat is
CC 0.327 sec(-1) with arachidoyl-CoA as substrate (PubMed:19376777).
CC {ECO:0000269|PubMed:11279212, ECO:0000269|PubMed:17557831,
CC ECO:0000269|PubMed:19376777};
CC pH dependence:
CC Optimum pH is 7.5 to 8.0. {ECO:0000269|PubMed:11279212};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000305|PubMed:11279212, ECO:0000305|PubMed:19376777}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11279212,
CC ECO:0000269|PubMed:17559874, ECO:0000269|PubMed:19376777}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17557831}.
CC Note=Distributed throughout the cytoplasm.
CC {ECO:0000269|PubMed:17557831}.
CC -!- SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent
CC aminotransferase family. {ECO:0000305}.
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DR EMBL; AB055142; BAB56013.1; -; Genomic_DNA.
DR EMBL; JABEOU010000017; NNG56642.1; -; Genomic_DNA.
DR EMBL; CP065713; QPT08440.1; -; Genomic_DNA.
DR RefSeq; WP_007405449.1; NZ_LDUA01000007.1.
DR PDB; 2JG2; X-ray; 1.30 A; A=1-420.
DR PDB; 2JGT; X-ray; 3.00 A; A/B=1-420.
DR PDB; 2W8J; X-ray; 1.50 A; A=2-420.
DR PDB; 2W8T; X-ray; 1.25 A; A=2-420.
DR PDB; 2W8U; X-ray; 1.50 A; A=2-420.
DR PDB; 2W8V; X-ray; 1.43 A; A=2-420.
DR PDB; 2W8W; X-ray; 2.14 A; A=2-420.
DR PDB; 2XBN; X-ray; 1.40 A; A=2-420.
DR PDB; 4BMK; X-ray; 1.62 A; A/B=2-420.
DR PDBsum; 2JG2; -.
DR PDBsum; 2JGT; -.
DR PDBsum; 2W8J; -.
DR PDBsum; 2W8T; -.
DR PDBsum; 2W8U; -.
DR PDBsum; 2W8V; -.
DR PDBsum; 2W8W; -.
DR PDBsum; 2XBN; -.
DR PDBsum; 4BMK; -.
DR SMR; Q93UV0; -.
DR ChEMBL; CHEMBL3217400; -.
DR EnsemblBacteria; QBE91942; QBE91942; DRN02_007885.
DR BRENDA; 2.3.1.50; 2280.
DR UniPathway; UPA00222; -.
DR EvolutionaryTrace; Q93UV0; -.
DR PRO; PR:Q93UV0; -.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0008483; F:transaminase activity; IEA:UniProtKB-KW.
DR GO; GO:0009058; P:biosynthetic process; IEA:InterPro.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR001917; Aminotrans_II_pyridoxalP_BS.
DR InterPro; IPR004839; Aminotransferase_I/II.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR Pfam; PF00155; Aminotran_1_2; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
DR PROSITE; PS00599; AA_TRANSFER_CLASS_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Cytoplasm; Direct protein sequencing;
KW Lipid metabolism; Pyridoxal phosphate; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:11279212"
FT CHAIN 2..420
FT /note="Serine palmitoyltransferase"
FT /id="PRO_0000456080"
FT BINDING 134..135
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:17559874,
FT ECO:0000269|PubMed:19376777, ECO:0007744|PDB:2JG2,
FT ECO:0007744|PDB:2W8T, ECO:0007744|PDB:2W8U,
FT ECO:0007744|PDB:2W8V"
FT BINDING 234
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:17559874,
FT ECO:0007744|PDB:2JG2"
FT BINDING 262
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:17559874,
FT ECO:0000269|PubMed:19376777, ECO:0007744|PDB:2JG2,
FT ECO:0007744|PDB:2W8T, ECO:0007744|PDB:2W8U,
FT ECO:0007744|PDB:2W8V"
FT BINDING 264
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:17559874,
FT ECO:0000269|PubMed:19376777, ECO:0007744|PDB:2JG2,
FT ECO:0007744|PDB:2W8T, ECO:0007744|PDB:2W8U,
FT ECO:0007744|PDB:2W8V"
FT MOD_RES 265
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000269|PubMed:17559874,
FT ECO:0000269|PubMed:19376777, ECO:0007744|PDB:2JG2,
FT ECO:0007744|PDB:2W8T, ECO:0007744|PDB:2W8U,
FT ECO:0007744|PDB:2W8V"
FT MUTAGEN 100
FT /note="N->C: 23-fold decrease in catalytic efficiency for
FT L-serine."
FT /evidence="ECO:0000269|PubMed:19376777"
FT MUTAGEN 100
FT /note="N->W: 147-fold decrease in catalytic efficiency for
FT L-serine. Affects the chemistry of the pyridoxal
FT phosphate."
FT /evidence="ECO:0000269|PubMed:19376777"
FT MUTAGEN 100
FT /note="N->Y: 410-fold decrease in catalytic efficiency for
FT L-serine. Affects the chemistry of the pyridoxal phosphate.
FT Is less able to stabilize a quinonoid intermediate."
FT /evidence="ECO:0000269|PubMed:19376777"
FT MUTAGEN 265
FT /note="K->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:23957439"
FT MUTAGEN 378
FT /note="R->A: 40-fold decrease in catalytic efficiency for
FT L-serine. Is less able to stabilize a quinonoid
FT intermediate."
FT /evidence="ECO:0000269|PubMed:19376777"
FT MUTAGEN 378
FT /note="R->N: 60-fold decrease in catalytic efficiency for
FT L-serine."
FT /evidence="ECO:0000269|PubMed:19376777"
SQ SEQUENCE 420 AA; 45042 MW; D36B6902D032DE1B CRC64;
MTEAAAQPHA LPADAPDIAP ERDLLSKFDG LIAERQKLLD SGVTDPFAIV MEQVKSPTEA
VIRGKDTILL GTYNYMGMTF DPDVIAAGKE ALEKFGSGTN GSRMLNGTFH DHMEVEQALR
DFYGTTGAIV FSTGYMANLG IISTLAGKGE YVILDADSHA SIYDGCQQGN AEIVRFRHNS
VEDLDKRLGR LPKEPAKLVV LEGVYSMLGD IAPLKEMVAV AKKHGAMVLV DEAHSMGFFG
PNGRGVYEAQ GLEGQIDFVV GTFSKSVGTV GGFVVSNHPK FEAVRLACRP YIFTASLPPS
VVATATTSIR KLMTAHEKRE RLWSNARALH GGLKAMGFRL GTETCDSAIV AVMLEDQEQA
AMMWQALLDG GLYVNMARPP ATPAGTFLLR CSICAEHTPA QIQTVLGMFQ AAGRAVGVIG
