NMT_YEAST
ID NMT_YEAST Reviewed; 455 AA.
AC P14743; D6VYJ8;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Glycylpeptide N-tetradecanoyltransferase;
DE EC=2.3.1.97 {ECO:0000269|PubMed:11478885, ECO:0000269|PubMed:3106975, ECO:0000269|PubMed:8430078, ECO:0000269|PubMed:8955162};
DE AltName: Full=Cell division control protein 72;
DE AltName: Full=Myristoyl-CoA:protein N-myristoyltransferase;
DE Short=NMT;
DE AltName: Full=Peptide N-myristoyltransferase;
GN Name=NMT1; Synonyms=CDC72; OrderedLocusNames=YLR195C; ORFNames=L8167.14;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 9-15; 132-138;
RP 198-211; 292-301; 323-337 AND 413-428.
RC STRAIN=ATCC 204511 / S288c / AB972;
RX PubMed=2644694; DOI=10.1126/science.2644694;
RA Duronio R.J., Towler D.A., Heuckeroth R.O., Gordon J.I.;
RT "Disruption of the yeast N-myristoyl transferase gene causes recessive
RT lethality.";
RL Science 243:796-800(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169871;
RA Johnston M., Hillier L.W., Riles L., Albermann K., Andre B., Ansorge W.,
RA Benes V., Brueckner M., Delius H., Dubois E., Duesterhoeft A.,
RA Entian K.-D., Floeth M., Goffeau A., Hebling U., Heumann K.,
RA Heuss-Neitzel D., Hilbert H., Hilger F., Kleine K., Koetter P., Louis E.J.,
RA Messenguy F., Mewes H.-W., Miosga T., Moestl D., Mueller-Auer S.,
RA Nentwich U., Obermaier B., Piravandi E., Pohl T.M., Portetelle D.,
RA Purnelle B., Rechmann S., Rieger M., Rinke M., Rose M., Scharfe M.,
RA Scherens B., Scholler P., Schwager C., Schwarz S., Underwood A.P.,
RA Urrestarazu L.A., Vandenbol M., Verhasselt P., Vierendeels F., Voet M.,
RA Volckaert G., Voss H., Wambutt R., Wedler E., Wedler H., Zimmermann F.K.,
RA Zollner A., Hani J., Hoheisel J.D.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XII.";
RL Nature 387:87-90(1997).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=3106975; DOI=10.1073/pnas.84.9.2708;
RA Towler D.A., Adams S.P., Eubanks S.R., Towery D.S., Jackson-Machelski E.,
RA Glaser L., Gordon J.I.;
RT "Purification and characterization of yeast myristoyl CoA:protein N-
RT myristoyltransferase.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:2708-2712(1987).
RN [5]
RP ERRATUM OF PUBMED:3106975.
RA Towler D.A., Adams S.P., Eubanks S.R., Towery D.S., Jackson-Machelski E.,
RA Glaser L., Gordon J.I.;
RL Proc. Natl. Acad. Sci. U.S.A. 84:7523-7523(1987).
RN [6]
RP MUTAGENESIS OF GLY-451.
RX PubMed=2045414; DOI=10.1083/jcb.113.6.1313;
RA Duronio R.J., Rudnick D.A., Johnson R.L., Johnson D.R., Gordon J.I.;
RT "Myristic acid auxotrophy caused by mutation of S. cerevisiae myristoyl-
RT CoA:protein N-myristoyltransferase.";
RL J. Cell Biol. 113:1313-1330(1991).
RN [7]
RP MUTAGENESIS OF LEU-99.
RX PubMed=8416952; DOI=10.1016/s0021-9258(18)54177-6;
RA Johnson D.R., Duronio R.J., Langner C.A., Rudnick D.A., Gordon J.I.;
RT "Genetic and biochemical studies of a mutant Saccharomyces cerevisiae
RT myristoyl-CoA:protein N-myristoyltransferase, nmt72pLeu99-->Pro, that
RT produces temperature-sensitive myristic acid auxotrophy.";
RL J. Biol. Chem. 268:483-494(1993).
RN [8]
RP CATALYTIC ACTIVITY.
RX PubMed=8430078; DOI=10.1073/pnas.90.3.1087;
RA Rudnick D.A., Rocque W.J., McWherter C.A., Toth M.V., Jackson-Machelski E.,
RA Gordon J.I.;
RT "Use of photoactivatable peptide substrates of Saccharomyces cerevisiae
RT myristoyl-CoA:protein N-myristoyltransferase (Nmt1p) to characterize a
RT myristoyl-CoA-Nmt1p-peptide ternary complex and to provide evidence for an
RT ordered reaction mechanism.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:1087-1091(1993).
RN [9]
RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF ALA-202; CYS-217; SER-328; ASN-404
RP AND ASN-426.
RX PubMed=8955162; DOI=10.1074/jbc.271.51.33131;
RA Zhang L., Jackson-Machelski E., Gordon J.I.;
RT "Biochemical studies of Saccharomyces cerevisiae myristoyl-coenzyme
RT A:protein N-myristoyltransferase mutants.";
RL J. Biol. Chem. 271:33131-33140(1996).
RN [10]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ASN-169;
RP PHE-170; LEU-171; THR-205 AND 454-MET-LEU-455, AND ACTIVE SITE.
RX PubMed=11478885; DOI=10.1021/bi0107997;
RA Farazi T.A., Manchester J.K., Waksman G., Gordon J.I.;
RT "Pre-steady-state kinetic studies of Saccharomyces cerevisiae
RT myristoylCoA:protein N-myristoyltransferase mutants identify residues
RT involved in catalysis.";
RL Biochemistry 40:9177-9186(2001).
RN [11]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 34-455 IN COMPLEX WITH
RP MYRISTOYL-COA AND INHIBITOR.
RX PubMed=9846880; DOI=10.1038/4202;
RA Bhatnagar R.S., Fuetterer K., Farazi T.A., Korolev S., Murray C.L.,
RA Jackson-Machelski E., Gokel G.W., Gordon J.I., Waksman G.;
RT "Structure of N-myristoyltransferase with bound myristoyl-CoA and peptide
RT substrate analogs.";
RL Nat. Struct. Biol. 5:1091-1097(1998).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 34-455 IN COMPLEX WITH
RP MYRISTOYL-COA AND SUBSTRATE.
RX PubMed=11371195; DOI=10.1021/bi0101401;
RA Farazi T.A., Waksman G., Gordon J.I.;
RT "Structures of Saccharomyces cerevisiae N-myristoyltransferase with bound
RT myristoylCoA and peptide provide insights about substrate recognition and
RT catalysis.";
RL Biochemistry 40:6335-6343(2001).
CC -!- FUNCTION: Adds a myristoyl group to the N-terminal glycine residue of
CC certain cellular proteins. Substrate specificity requires an N-terminal
CC glycine in the nascent polypeptide substrates. Uncharged amino acids
CC are preferred at position 2 while neutral residues are favored at
CC positions 3 and 4. Ser is present at position 5 in almost all known N-
CC myristoyl proteins and Lys is commonly encountered at postion 6.
CC {ECO:0000269|PubMed:3106975}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-terminal glycyl-[protein] + tetradecanoyl-CoA = CoA + H(+) +
CC N-tetradecanoylglycyl-[protein]; Xref=Rhea:RHEA:15521, Rhea:RHEA-
CC COMP:12666, Rhea:RHEA-COMP:12667, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57385, ChEBI:CHEBI:64723,
CC ChEBI:CHEBI:133050; EC=2.3.1.97;
CC Evidence={ECO:0000269|PubMed:11478885, ECO:0000269|PubMed:3106975,
CC ECO:0000269|PubMed:8430078, ECO:0000269|PubMed:8955162};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15522;
CC Evidence={ECO:0000269|PubMed:11478885, ECO:0000269|PubMed:3106975,
CC ECO:0000269|PubMed:8430078, ECO:0000269|PubMed:8955162};
CC -!- ACTIVITY REGULATION: Inhibited by diethylpyrocarbonate. Competitively
CC inhibited by S-(2-oxo)pentadecyl-CoA, a non hydrolysable myristoyl-CoA
CC analog, and by SC-58272, a peptidomimetic derived from the N-terminal
CC sequence of a natural substrate. {ECO:0000269|PubMed:8955162}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.4 uM for myristoyl-CoA {ECO:0000269|PubMed:11478885,
CC ECO:0000269|PubMed:3106975};
CC pH dependence:
CC Optimum pH is 7.5-8.0. {ECO:0000269|PubMed:11478885,
CC ECO:0000269|PubMed:3106975};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:11371195,
CC ECO:0000269|PubMed:9846880}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}.
CC -!- PTM: The N-terminus is blocked. {ECO:0000305|PubMed:2644694}.
CC -!- MISCELLANEOUS: Has an ordered Bi-Bi kinetic mechanism, with myristoyl-
CC CoA binding taking place prior to peptide binding and CoA release
CC occurring before acylated peptide release. Cooperative interactions
CC between the acyl-CoA and peptide binding sites of NMT contribute to its
CC extraordinary chain-length specificity. {ECO:0000305|PubMed:8430078}.
CC -!- SIMILARITY: Belongs to the NMT family. {ECO:0000305}.
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DR EMBL; M23726; AAA34815.1; -; Genomic_DNA.
DR EMBL; U14913; AAB67436.1; -; Genomic_DNA.
DR EMBL; BK006945; DAA09514.1; -; Genomic_DNA.
DR PIR; A40163; A40163.
DR RefSeq; NP_013296.1; NM_001182082.1.
DR PDB; 1IIC; X-ray; 2.20 A; A/B=34-455.
DR PDB; 1IID; X-ray; 2.50 A; A=34-455.
DR PDB; 2NMT; X-ray; 2.90 A; A=34-455.
DR PDB; 2P6E; X-ray; 2.90 A; A/B/C/D/E/F=1-455.
DR PDB; 2P6F; X-ray; 3.10 A; A/B/C/D/E/F=1-455.
DR PDB; 2P6G; X-ray; 3.00 A; A/B/C/D/E/F=1-455.
DR PDBsum; 1IIC; -.
DR PDBsum; 1IID; -.
DR PDBsum; 2NMT; -.
DR PDBsum; 2P6E; -.
DR PDBsum; 2P6F; -.
DR PDBsum; 2P6G; -.
DR AlphaFoldDB; P14743; -.
DR SMR; P14743; -.
DR BioGRID; 31465; 305.
DR STRING; 4932.YLR195C; -.
DR BindingDB; P14743; -.
DR ChEMBL; CHEMBL5484; -.
DR MaxQB; P14743; -.
DR PaxDb; P14743; -.
DR PRIDE; P14743; -.
DR EnsemblFungi; YLR195C_mRNA; YLR195C; YLR195C.
DR GeneID; 850892; -.
DR KEGG; sce:YLR195C; -.
DR SGD; S000004185; NMT1.
DR VEuPathDB; FungiDB:YLR195C; -.
DR eggNOG; KOG2779; Eukaryota.
DR GeneTree; ENSGT00390000017837; -.
DR HOGENOM; CLU_022882_2_0_1; -.
DR InParanoid; P14743; -.
DR OMA; RDWHVGV; -.
DR BioCyc; YEAST:YLR195C-MON; -.
DR BRENDA; 2.3.1.97; 984.
DR Reactome; R-SCE-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR EvolutionaryTrace; P14743; -.
DR PRO; PR:P14743; -.
DR Proteomes; UP000002311; Chromosome XII.
DR RNAct; P14743; protein.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:SGD.
DR GO; GO:0004379; F:glycylpeptide N-tetradecanoyltransferase activity; IMP:SGD.
DR GO; GO:0018008; P:N-terminal peptidyl-glycine N-myristoylation; IBA:GO_Central.
DR InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR000903; NMT.
DR InterPro; IPR022677; NMT_C.
DR InterPro; IPR022678; NMT_CS.
DR InterPro; IPR022676; NMT_N.
DR PANTHER; PTHR11377; PTHR11377; 1.
DR Pfam; PF01233; NMT; 1.
DR Pfam; PF02799; NMT_C; 1.
DR PIRSF; PIRSF015892; N-myristl_transf; 1.
DR SUPFAM; SSF55729; SSF55729; 2.
DR PROSITE; PS00975; NMT_1; 1.
DR PROSITE; PS00976; NMT_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Cytoplasm; Direct protein sequencing;
KW Reference proteome; Transferase.
FT CHAIN 1..455
FT /note="Glycylpeptide N-tetradecanoyltransferase"
FT /id="PRO_0000064248"
FT REGION 168..204
FT /note="Myristoyl CoA-binding"
FT ACT_SITE 455
FT /note="Proton acceptor; via carboxylate"
FT /evidence="ECO:0000269|PubMed:11478885"
FT BINDING 38..41
FT /ligand="tetradecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57385"
FT MUTAGEN 99
FT /note="L->P: In NMT1-72; temperature-sensitive mutant with
FT myristic acid auxotrophy."
FT /evidence="ECO:0000269|PubMed:8416952"
FT MUTAGEN 169
FT /note="N->L: Reduces the chemical transformation rate; when
FT associated with A-205."
FT /evidence="ECO:0000269|PubMed:11478885"
FT MUTAGEN 170
FT /note="F->A: Reduces the chemical transformation rate; when
FT associated with A-171."
FT /evidence="ECO:0000269|PubMed:11478885"
FT MUTAGEN 171
FT /note="L->A: Reduces the chemical transformation rate; when
FT associated with A-170."
FT /evidence="ECO:0000269|PubMed:11478885"
FT MUTAGEN 202
FT /note="A->T: Reduces affinity for both substrate and
FT myristoyl-CoA."
FT /evidence="ECO:0000269|PubMed:8955162"
FT MUTAGEN 205
FT /note="T->A: Reduces the chemical transformation rate; when
FT associated with L-169."
FT /evidence="ECO:0000269|PubMed:11478885"
FT MUTAGEN 217
FT /note="C->R: Reduces affinity for substrate, but not for
FT myristoyl-CoA."
FT /evidence="ECO:0000269|PubMed:8955162"
FT MUTAGEN 328
FT /note="S->P: Moderately reduces affinity for myristoyl-CoA,
FT but not for substrate."
FT /evidence="ECO:0000269|PubMed:8955162"
FT MUTAGEN 404
FT /note="N->Y: Moderately reduces affinity for substrate, but
FT not for myristoyl-CoA."
FT /evidence="ECO:0000269|PubMed:8955162"
FT MUTAGEN 426
FT /note="N->I: Reduces affinity for myristoyl-CoA, but not
FT for substrate."
FT /evidence="ECO:0000269|PubMed:8955162"
FT MUTAGEN 451
FT /note="G->D: In NMT1-181; temperature-sensitive with
FT myristic acid auxotrophy. Reduces affinity for myristoyl-
FT CoA."
FT /evidence="ECO:0000269|PubMed:2045414"
FT MUTAGEN 454..455
FT /note="Missing: Reduces chemical transformation rate 400-
FT fold."
FT /evidence="ECO:0000269|PubMed:11478885"
FT HELIX 6..17
FT /evidence="ECO:0007829|PDB:2P6E"
FT HELIX 35..37
FT /evidence="ECO:0007829|PDB:2NMT"
FT HELIX 41..43
FT /evidence="ECO:0007829|PDB:1IIC"
FT STRAND 57..60
FT /evidence="ECO:0007829|PDB:1IIC"
FT HELIX 65..67
FT /evidence="ECO:0007829|PDB:1IIC"
FT STRAND 79..83
FT /evidence="ECO:0007829|PDB:1IIC"
FT STRAND 86..88
FT /evidence="ECO:0007829|PDB:2P6G"
FT HELIX 89..102
FT /evidence="ECO:0007829|PDB:1IIC"
FT STRAND 103..105
FT /evidence="ECO:0007829|PDB:1IIC"
FT HELIX 107..109
FT /evidence="ECO:0007829|PDB:1IIC"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:1IIC"
FT HELIX 117..124
FT /evidence="ECO:0007829|PDB:1IIC"
FT HELIX 131..133
FT /evidence="ECO:0007829|PDB:1IIC"
FT STRAND 134..139
FT /evidence="ECO:0007829|PDB:1IIC"
FT TURN 140..142
FT /evidence="ECO:0007829|PDB:1IIC"
FT STRAND 145..158
FT /evidence="ECO:0007829|PDB:1IIC"
FT STRAND 161..173
FT /evidence="ECO:0007829|PDB:1IIC"
FT HELIX 175..177
FT /evidence="ECO:0007829|PDB:1IIC"
FT STRAND 179..181
FT /evidence="ECO:0007829|PDB:1IID"
FT HELIX 183..195
FT /evidence="ECO:0007829|PDB:1IIC"
FT TURN 196..198
FT /evidence="ECO:0007829|PDB:1IIC"
FT STRAND 202..208
FT /evidence="ECO:0007829|PDB:1IIC"
FT STRAND 214..225
FT /evidence="ECO:0007829|PDB:1IIC"
FT HELIX 226..231
FT /evidence="ECO:0007829|PDB:1IIC"
FT HELIX 239..241
FT /evidence="ECO:0007829|PDB:1IID"
FT HELIX 243..250
FT /evidence="ECO:0007829|PDB:1IIC"
FT STRAND 261..263
FT /evidence="ECO:0007829|PDB:1IIC"
FT HELIX 266..268
FT /evidence="ECO:0007829|PDB:1IIC"
FT HELIX 269..280
FT /evidence="ECO:0007829|PDB:1IIC"
FT STRAND 283..287
FT /evidence="ECO:0007829|PDB:1IIC"
FT HELIX 291..298
FT /evidence="ECO:0007829|PDB:1IIC"
FT STRAND 301..303
FT /evidence="ECO:0007829|PDB:2P6E"
FT HELIX 306..308
FT /evidence="ECO:0007829|PDB:1IIC"
FT STRAND 311..317
FT /evidence="ECO:0007829|PDB:1IIC"
FT STRAND 323..331
FT /evidence="ECO:0007829|PDB:1IIC"
FT STRAND 334..336
FT /evidence="ECO:0007829|PDB:1IIC"
FT STRAND 343..345
FT /evidence="ECO:0007829|PDB:1IIC"
FT STRAND 347..355
FT /evidence="ECO:0007829|PDB:1IIC"
FT TURN 357..360
FT /evidence="ECO:0007829|PDB:1IIC"
FT HELIX 367..390
FT /evidence="ECO:0007829|PDB:1IIC"
FT STRAND 394..400
FT /evidence="ECO:0007829|PDB:1IIC"
FT HELIX 404..406
FT /evidence="ECO:0007829|PDB:1IIC"
FT TURN 407..412
FT /evidence="ECO:0007829|PDB:1IIC"
FT STRAND 414..425
FT /evidence="ECO:0007829|PDB:1IIC"
FT STRAND 434..436
FT /evidence="ECO:0007829|PDB:1IIC"
FT STRAND 440..442
FT /evidence="ECO:0007829|PDB:1IIC"
FT TURN 444..446
FT /evidence="ECO:0007829|PDB:1IIC"
SQ SEQUENCE 455 AA; 52838 MW; 0424CA3978F76AE6 CRC64;
MSEEDKAKKL ENLLKLLQLN NDDTSKFTQE QKKAMKDHKF WRTQPVKDFD EKVVEEGPID
KPKTPEDISD KPLPLLSSFE WCSIDVDNKK QLEDVFVLLN ENYVEDRDAG FRFNYTKEFF
NWALKSPGWK KDWHIGVRVK ETQKLVAFIS AIPVTLGVRG KQVPSVEINF LCVHKQLRSK
RLTPVLIKEI TRRVNKCDIW HALYTAGIVL PAPVSTCRYT HRPLNWKKLY EVDFTGLPDG
HTEEDMIAEN ALPAKTKTAG LRKLKKEDID QVFELFKRYQ SRFELIQIFT KEEFEHNFIG
EESLPLDKQV IFSYVVEQPD GKITDFFSFY SLPFTILNNT KYKDLGIGYL YYYATDADFQ
FKDRFDPKAT KALKTRLCEL IYDACILAKN ANMDVFNALT SQDNTLFLDD LKFGPGDGFL
NFYLFNYRAK PITGGLNPDN SNDIKRRSNV GVVML
