PAM_TAXCA
ID PAM_TAXCA Reviewed; 698 AA.
AC Q6GZ04;
DT 03-SEP-2014, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=Phenylalanine aminomutase (L-beta-phenylalanine forming);
DE EC=5.4.3.10 {ECO:0000269|PubMed:21361343};
DE AltName: Full=Phenylalanine ammonia-lyase;
DE EC=4.3.1.24 {ECO:0000269|PubMed:21361343};
GN Name=pam;
OS Taxus canadensis (Canadian yew).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Pinopsida; Pinidae; Conifers II; Cupressales; Taxaceae;
OC Taxus.
OX NCBI_TaxID=88032;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15178753; DOI=10.1073/pnas.0403009101;
RA Jennewein S., Wildung M.R., Chau M., Walker K., Croteau R.;
RT "Random sequencing of an induced Taxus cell cDNA library for identification
RT of clones involved in Taxol biosynthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:9149-9154(2004).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.38 ANGSTROMS) IN COMPLEX WITH TRANS-CINNAMATE,
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, PTM,
RP AND MUTAGENESIS OF TYR-80 AND LEU-104.
RX PubMed=21361343; DOI=10.1021/bi102067r;
RA Feng L., Wanninayake U., Strom S., Geiger J., Walker K.D.;
RT "Mechanistic, mutational, and structural evaluation of a Taxus
RT phenylalanine aminomutase.";
RL Biochemistry 50:2919-2930(2011).
CC -!- FUNCTION: Phenylalanine aminomutase that catalyzes the rearrangement of
CC L-phenylalanine to R-beta-phenylalanine. Catalyzes the first committed
CC step in the biosynthesis of the side chain of the alkaloid taxol
CC (paclitaxel), a widely-used compound with antitumor activity. Also has
CC low phenylalanine ammonia-lyase activity.
CC {ECO:0000269|PubMed:21361343}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-phenylalanine = L-beta-phenylalanine; Xref=Rhea:RHEA:34395,
CC ChEBI:CHEBI:58095, ChEBI:CHEBI:67158; EC=5.4.3.10;
CC Evidence={ECO:0000269|PubMed:21361343};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-phenylalanine = (E)-cinnamate + NH4(+);
CC Xref=Rhea:RHEA:21384, ChEBI:CHEBI:15669, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:58095; EC=4.3.1.24;
CC Evidence={ECO:0000269|PubMed:21361343};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.057 mM for L-phenylalanine {ECO:0000269|PubMed:21361343};
CC Note=kcat is 0.053 sec(-1) for L-phenylalanine.
CC {ECO:0000269|PubMed:21361343};
CC -!- PATHWAY: Alkaloid biosynthesis; taxol biosynthesis. {ECO:0000305}.
CC -!- PATHWAY: Phenylpropanoid metabolism; trans-cinnamate biosynthesis;
CC trans-cinnamate from L-phenylalanine: step 1/1.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:21361343}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- PTM: Contains an active site 4-methylidene-imidazol-5-one (MIO), which
CC is formed autocatalytically by cyclization and dehydration of residues
CC Ala-Ser-Gly. {ECO:0000250|UniProtKB:Q68G84}.
CC -!- SIMILARITY: Belongs to the PAL/histidase family. {ECO:0000305}.
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DR EMBL; AY582743; AAT47186.1; -; mRNA.
DR PDB; 3NZ4; X-ray; 2.38 A; A/B=1-698.
DR PDBsum; 3NZ4; -.
DR AlphaFoldDB; Q6GZ04; -.
DR SMR; Q6GZ04; -.
DR KEGG; ag:AAT47186; -.
DR BioCyc; MetaCyc:MON-17466; -.
DR BRENDA; 5.4.3.10; 6224.
DR UniPathway; UPA00713; UER00725.
DR UniPathway; UPA00842; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016869; F:intramolecular transferase activity, transferring amino groups; IDA:UniProtKB.
DR GO; GO:0045548; F:phenylalanine ammonia-lyase activity; IEA:UniProtKB-EC.
DR GO; GO:0009821; P:alkaloid biosynthetic process; TAS:UniProtKB.
DR GO; GO:0009800; P:cinnamic acid biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006559; P:L-phenylalanine catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006558; P:L-phenylalanine metabolic process; IDA:UniProtKB.
DR GO; GO:0042617; P:paclitaxel biosynthetic process; TAS:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR CDD; cd00332; PAL-HAL; 1.
DR Gene3D; 1.10.274.20; -; 1.
DR Gene3D; 1.10.275.10; -; 1.
DR InterPro; IPR001106; Aromatic_Lyase.
DR InterPro; IPR024083; Fumarase/histidase_N.
DR InterPro; IPR008948; L-Aspartase-like.
DR InterPro; IPR022313; Phe/His_NH3-lyase_AS.
DR InterPro; IPR005922; Phe_NH3-lyase.
DR InterPro; IPR023144; Phe_NH3-lyase_shielding_dom_sf.
DR InterPro; IPR031008; Taxol_Phe_23mut.
DR PANTHER; PTHR10362; PTHR10362; 1.
DR Pfam; PF00221; Lyase_aromatic; 1.
DR SUPFAM; SSF48557; SSF48557; 1.
DR TIGRFAMs; TIGR01226; phe_am_lyase; 1.
DR TIGRFAMs; TIGR04473; taxol_Phe_23mut; 1.
DR PROSITE; PS00488; PAL_HISTIDASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alkaloid metabolism; Cytoplasm; Isomerase; Lyase;
KW Phenylalanine catabolism; Phenylpropanoid metabolism; Taxol biosynthesis.
FT CHAIN 1..698
FT /note="Phenylalanine aminomutase (L-beta-phenylalanine
FT forming)"
FT /id="PRO_0000429969"
FT ACT_SITE 80
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q68G84"
FT BINDING 231
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q68G84"
FT BINDING 319
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q68G84"
FT BINDING 325
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q68G84"
FT BINDING 355
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q68G84"
FT BINDING 458
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q68G84"
FT MOD_RES 176
FT /note="2,3-didehydroalanine (Ser)"
FT /evidence="ECO:0000250|UniProtKB:Q68G84"
FT CROSSLNK 175..177
FT /note="5-imidazolinone (Ala-Gly)"
FT /evidence="ECO:0000250|UniProtKB:Q68G84"
FT MUTAGEN 80
FT /note="Y->F: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:21361343"
FT MUTAGEN 104
FT /note="L->A: Decreases enzyme activity."
FT /evidence="ECO:0000269|PubMed:21361343"
FT HELIX 10..23
FT /evidence="ECO:0007829|PDB:3NZ4"
FT STRAND 26..33
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 37..45
FT /evidence="ECO:0007829|PDB:3NZ4"
FT STRAND 50..53
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 55..74
FT /evidence="ECO:0007829|PDB:3NZ4"
FT TURN 81..83
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 87..89
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 97..108
FT /evidence="ECO:0007829|PDB:3NZ4"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 126..140
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 149..160
FT /evidence="ECO:0007829|PDB:3NZ4"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 179..189
FT /evidence="ECO:0007829|PDB:3NZ4"
FT STRAND 195..202
FT /evidence="ECO:0007829|PDB:3NZ4"
FT STRAND 204..206
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 207..213
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 225..230
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 234..265
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 269..272
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 274..278
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 283..296
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 300..309
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 313..315
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 322..325
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 327..349
FT /evidence="ECO:0007829|PDB:3NZ4"
FT STRAND 355..359
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 360..362
FT /evidence="ECO:0007829|PDB:3NZ4"
FT STRAND 364..366
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 374..402
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 404..407
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 412..414
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 420..422
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 427..443
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 448..450
FT /evidence="ECO:0007829|PDB:3NZ4"
FT TURN 455..458
FT /evidence="ECO:0007829|PDB:3NZ4"
FT STRAND 459..461
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 465..517
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 522..534
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 537..539
FT /evidence="ECO:0007829|PDB:3NZ4"
FT TURN 540..542
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 550..565
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 574..603
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 620..622
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 626..633
FT /evidence="ECO:0007829|PDB:3NZ4"
FT TURN 634..637
FT /evidence="ECO:0007829|PDB:3NZ4"
FT STRAND 643..645
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 649..662
FT /evidence="ECO:0007829|PDB:3NZ4"
FT HELIX 666..673
FT /evidence="ECO:0007829|PDB:3NZ4"
SQ SEQUENCE 698 AA; 76532 MW; BE106526C9AA891C CRC64;
MGFAVESRSH VKDILGLINT FNEVKKITVD GTTPITVAHV AALARRHDVK VALEAEQCRA
RVETCSSWVQ RKAEDGADIY GVTTGFGACS SRRTNQLSEL QESLIRCLLA GVFTKGCASS
VDELPATATR SAMLLRLNSF TYGCSGIRWE VMEALEKLLN SNVSPKVPLR GSVSASGDLI
PLAYIAGLLI GKPSVVARIG DDVEVPAPEA LSRVGLRPFK LQAKEGLALV NGTSFATALA
STVMYDANVL LLLVETLCGM FCEVIFGREE FAHPLIHKVK PHPGQIESAE LLEWLLRSSP
FQDLSREYYS IDKLKKPKQD RYALRSSPQW LAPLVQTIRD ATTTVETEVN SANDNPIIDH
ANDRALHGAN FQGSAVGFYM DYVRIAVAGL GKLLFAQFTE LMIEYYSNGL PGNLSLGPDL
SVDYGLKGLD IAMAAYSSEL QYLANPVTTH VHSAEQHNQD INSLALISAR KTEEALDILK
LMIASHLTAM CQAVDLRQLE EALVKVVENV VSTLADECGL PNDTKARLLY VAKAVPVYTY
LESPCDPTLP LLLGLEQSCF GSILALHKKD GIETDTLVDR LAEFEKRLSD RLENEMTAVR
VLYEKKGHKT ADNNDALVRI QGSRFLPFYR FVREELDTGV MSARREQTPQ EDVQKVFDAI
ADGRITVPLL HCLQGFLGQP NGCANGVESF QSVWNKSA
