EzCatDB: D00413
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DB codeD00413
RLCP classification3.1147.47600.180 : Transfer
CATH domainDomain 13.40.630.30 : AminopeptidaseCatalytic domain
Domain 23.40.630.30 : Aminopeptidase
E.C.2.3.1.97
CSA2nmt

CATH domainRelated DB codes (homologues)
3.40.630.30 : AminopeptidaseM00165,S00409,S00410,T00034

Enzyme Name
UniProtKBKEGG

P30418P14743
Protein nameGlycylpeptide N-tetradecanoyltransferaseGlycylpeptide N-tetradecanoyltransferaseglycylpeptide N-tetradecanoyltransferase
peptide N-myristoyltransferase
myristoyl-CoA-protein N-myristoyltransferase
myristoyl-coenzyme A:protein N-myristoyl transferase
myristoylating enzymes
protein N-myristoyltransferase
SynonymsEC 2.3.1.97
Myristoyl-CoA:protein N-myristoyltransferase
NMT
Peptide N-myristoyltransferase
EC 2.3.1.97
Cell division control protein 72
Myristoyl-CoA:protein N-myristoyltransferase
NMT
Peptide N-myristoyltransferase
RefSeqXP_722713.1 (Protein)
XM_717620.1 (DNA/RNA sequence)
XP_722859.1 (Protein)
XM_717766.1 (DNA/RNA sequence)
NP_013296.1 (Protein)
NM_001182082.1 (DNA/RNA sequence)
PfamPF01233 (NMT)
PF02799 (NMT_C)
[Graphical view]
PF01233 (NMT)
PF02799 (NMT_C)
[Graphical view]


UniProtKB:Accession NumberP30418P14743
Entry nameNMT_CANALNMT_YEAST
ActivityTetradecanoyl-CoA + glycylpeptide = CoA + N- tetradecanoylglycylpeptide.Tetradecanoyl-CoA + glycylpeptide = CoA + N- tetradecanoylglycylpeptide.
SubunitMonomer.Monomer.
Subcellular locationCytoplasm.Cytoplasm.
Cofactor


Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC02593C02038C00010C03881
CompoundTetradecanoyl-CoAGlycylpeptideCoAN-Tetradecanoylglycylpeptide
Typeamine group,carbohydrate,lipid,nucleotide,peptide/protein,sulfide groupamine group,carboxyl group,peptide/proteinamine group,carbohydrate,nucleotide,peptide/protein,sulfhydryl groupcarboxyl group,lipid,peptide/protein
ChEBI15532

15346

PubChem65113
11966124

87642
6816

            
1iykA01Bound:MYAUnboundUnboundUnbound
1iykB01Bound:MYAUnboundUnboundUnbound
1iylA01UnboundUnboundUnboundUnbound
1iylB01UnboundUnboundUnboundUnbound
1iylC01UnboundUnboundUnboundUnbound
1iylD01UnboundUnboundUnboundUnbound
1nmtA01UnboundUnboundUnboundUnbound
1nmtB01UnboundUnboundUnboundUnbound
1nmtC01UnboundUnboundUnboundUnbound
1iicA01Bound:MYAUnboundUnboundUnbound
1iicB01Bound:MYAUnboundUnboundUnbound
1iidA01Analogue:NHMUnboundUnboundUnbound
2nmtA01Analogue:NHMUnboundUnboundUnbound
1iykA02UnboundAnalogue:MIMUnboundUnbound
1iykB02UnboundAnalogue:MIMUnboundUnbound
1iylA02UnboundAnalogue:R64UnboundUnbound
1iylB02UnboundAnalogue:R64UnboundUnbound
1iylC02UnboundAnalogue:R64UnboundUnbound
1iylD02UnboundAnalogue:R64UnboundUnbound
1nmtA02UnboundUnboundUnboundUnbound
1nmtB02UnboundUnboundUnboundUnbound
1nmtC02UnboundUnboundUnboundUnbound
1iicA02UnboundUnboundUnboundUnbound
1iicB02UnboundUnboundUnboundUnbound
1iidA02UnboundBound:GLY-LEU-TYR-ALA-SER-LYS-LEU-ALA(chain O)UnboundUnbound
2nmtA02UnboundAnalogue:MIMUnboundUnbound

Active-site residues
resource
literature [16], [12]
pdbCatalytic residuesMain-chain involved in catalysis
          
1iykA01ASN 175;THR 211
PHE 176;LEU 177;THR 211
1iykB01ASN 175;THR 211
PHE 176;LEU 177;THR 211
1iylA01ASN 175;THR 211
PHE 176;LEU 177;THR 211
1iylB01ASN 175;THR 211
PHE 176;LEU 177;THR 211
1iylC01ASN 175;THR 211
PHE 176;LEU 177;THR 211
1iylD01ASN 175;THR 211
PHE 176;LEU 177;THR 211
1nmtA01ASN 175;THR 211
PHE 176;LEU 177;THR 211
1nmtB01ASN 175;THR 211
PHE 176;LEU 177;THR 211
1nmtC01ASN 175;THR 211
PHE 176;LEU 177;THR 211
1iicA01ASN 169;THR 205
PHE 170;LEU 171;THR 205
1iicB01ASN 169;THR 205
PHE 170;LEU 171;THR 205
1iidA01ASN 169;THR 205
PHE 170;LEU 171;THR 205
2nmtA01ASN 169;THR 205
PHE 170;LEU 171;THR 205
1iykA02 
LEU 451
1iykB02 
LEU 451
1iylA02 
LEU 451
1iylB02 
LEU 451
1iylC02 
LEU 451
1iylD02 
LEU 451
1nmtA02 
LEU 451
1nmtB02 
LEU 451
1nmtC02 
LEU 451
1iicA02 
LEU 455
1iicB02 
LEU 455
1iidA02 
LEU 455
2nmtA02 
LEU 455

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[12]Fig.4, p.30891-308924
[16]Fig.5b, p.10943
[17]p.216-217
[18]Fig.4, p.14933-149343
[19]Fig.6, p.169-1703
[20]p.15814
[25]Fig.3, Fig.4, p.6341-63423

references
[1]
CommentsMUTAGENESIS OF GLY-451
PubMed ID2045414
JournalJ Cell Biol
Year1991
Volume113
Pages1313-30
AuthorsDuronio RJ, Rudnick DA, Johnson RL, Johnson DR, Gordon JI
TitleMyristic acid auxotrophy caused by mutation of S. cerevisiae myristoyl-CoA:protein N-myristoyltransferase.
Related UniProtKBP14743
[2]
PubMed ID2033063
JournalJ Biol Chem
Year1991
Volume266
Pages9732-9
AuthorsRudnick DA, McWherter CA, Rocque WJ, Lennon PJ, Getman DP, Gordon JI
TitleKinetic and structural evidence for a sequential ordered Bi Bi mechanism of catalysis by Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase.
[3]
PubMed ID1999191
JournalEur J Biochem
Year1991
Volume195
Pages699-705
AuthorsWagner AP, Retey J
TitleSynthesis of myristoyl-carba(dethia)-coenzyme A and S-(3-oxohexadecyl)-coenzyme A, two potent inhibitors of myristoyl-CoA:protein N-myristoyltransferase.
[4]
PubMed ID1559967
JournalJ Biol Chem
Year1992
Volume267
Pages7224-39
AuthorsDevadas B, Lu T, Katoh A, Kishore NS, Wade AC, Mehta PP, Rudnick DA, Bryant ML, Adams SP, Li Q, et al
TitleSubstrate specificity of Saccharomyces cerevisiae myristoyl-CoA: protein N-myristoyltransferase. Analysis of fatty acid analogs containing carbonyl groups, nitrogen heteroatoms, and nitrogen heterocycles in an in vitro enzyme assay and subsequent identification of inhibitors of human immunodeficiency virus I replication.
[5]
CommentsCHARACTERIZATION
PubMed ID8430078
JournalProc Natl Acad Sci U S A
Year1993
Volume90
Pages1087-91
AuthorsRudnick DA, Rocque WJ, McWherter CA, Toth MV, Jackson-Machelski E, Gordon JI
TitleUse of photoactivatable peptide substrates of Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase (Nmt1p) to characterize a myristoyl-CoA-Nmt1p-peptide ternary complex and to provide evidence for an ordered reaction mechanism.
Related UniProtKBP14743
[6]
CommentsMUTAGENESIS OF LEU-99
PubMed ID8416952
JournalJ Biol Chem
Year1993
Volume268
Pages483-94
AuthorsJohnson DR, Duronio RJ, Langner CA, Rudnick DA, Gordon JI
TitleGenetic and biochemical studies of a mutant Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase, nmt72pLeu99-->Pro, that produces temperature-sensitive myristic acid auxotrophy.
Related UniProtKBP14743
[7]
PubMed ID8486723
JournalJ Biol Chem
Year1993
Volume268
Pages9964-71
AuthorsRocque WJ, McWherter CA, Wood DC, Gordon JI
TitleA comparative analysis of the kinetic mechanism and peptide substrate specificity of human and Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase.
[8]
PubMed ID8322618
JournalAdv Enzymol Relat Areas Mol Biol
Year1993
Volume67
Pages375-430
AuthorsRudnick DA, McWherter CA, Gokel GW, Gordon JI
TitleMyristoylCoA:protein N-myristoyltransferase.
[9]
PubMed ID8169796
JournalJ Pharm Sci
Year1994
Volume83
Pages233-8
AuthorsZheng GQ, Hu X, Cassady JM, Paige LA, Geahlen RL
TitleSynthesis of myristoyl CoA analogues and myristoyl peptides as inhibitors of myristoyl CoA:protein N-myristoyltransferase.
[10]
PubMed ID8157630
JournalJ Biol Chem
Year1994
Volume269
Pages11045-53
AuthorsBhatnagar RS, Jackson-Machelski E, McWherter CA, Gordon JI
TitleIsothermal titration calorimetric studies of Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase. Determinants of binding energy and catalytic discrimination among acyl-CoA and peptide ligands.
[11]
PubMed ID8300631
JournalJ Biol Chem
Year1994
Volume269
Pages2996-3009
AuthorsLodge JK, Johnson RL, Weinberg RA, Gordon JI
TitleComparison of myristoyl-CoA:protein N-myristoyltransferases from three pathogenic fungi: Cryptococcus neoformans, Histoplasma capsulatum, and Candida albicans.
[12]
PubMed ID7983020
JournalJ Biol Chem
Year1994
Volume269
Pages30888-92
AuthorsPeseckis SM, Resh MD
TitleFatty acyl transfer by human N-myristyl transferase is dependent upon conserved cysteine and histidine residues.
[13]
PubMed ID9154965
JournalJ Med Chem
Year1997
Volume40
Pages1422-38
AuthorsNagarajan SR, Devadas B, Zupec ME, Freeman SK, Brown DL, Lu HF, Mehta PP, Kishore NS, McWherter CA, Getman DP, Gordon JI, Sikorski JA
TitleConformationally constrained [p-(omega-aminoalkyl)phenacetyl]-L-seryl-L-lysyl dipeptide amides as potent peptidomimetic inhibitors of Candida albicans and human myristoyl-CoA:protein N-myristoyl transferase.
[14]
PubMed ID9044045
JournalJ Cell Sci
Year1997
Volume110
Pages149-56
AuthorsNtwasa M, Egerton M, Gay NJ
TitleSequence and expression of Drosophila myristoyl-CoA: protein N-myristoyl transferase: evidence for proteolytic processing and membrane localisation.
[15]
PubMed ID9184150
JournalBiochemistry
Year1997
Volume36
Pages6700-8
AuthorsBhatnagar RS, Schall OF, Jackson-Machelski E, Sikorski JA, Devadas B, Gokel GW, Gordon JI
TitleTitration calorimetric analysis of AcylCoA recognition by myristoylCoA:protein N-myristoyltransferase.
[16]
CommentsX-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS)
PubMed ID9846880
JournalNat Struct Biol
Year1998
Volume5
Pages1091-7
AuthorsBhatnagar RS, Futterer K, Farazi TA, Korolev S, Murray CL, Jackson-Machelski E, Gokel GW, Gordon JI, Waksman G
TitleStructure of N-myristoyltransferase with bound myristoylCoA and peptide substrate analogs.
Related PDB2nmt
Related UniProtKBP14743
[17]
PubMed ID9501915
JournalNat Struct Biol
Year1998
Volume5
Pages213-21
AuthorsWeston SA, Camble R, Colls J, Rosenbrock G, Taylor I, Egerton M, Tucker AD, Tunnicliffe A, Mistry A, Mancia F, de la Fortelle E, Irwin J, Bricogne G, Pauptit RA
TitleCrystal structure of the anti-fungal target N-myristoyl transferase.
Related PDB1nmt
[18]
PubMed ID9778369
JournalBiochemistry
Year1998
Volume37
Pages14928-36
AuthorsRaju RV, Datla RS, Warrington RC, Sharma RK
TitleEffects of L-histidine and its structural analogues on human N-myristoyltransferase activity and importance of EEVEH amino acid sequence for enzyme activity.
[19]
PubMed ID10570244
JournalBiochim Biophys Acta
Year1999
Volume1441
Pages162-72
AuthorsBhatnagar RS, Futterer K, Waksman G, Gordon JIThe structure of myristoyl-CoA:protein N-myristoyltransferase
TitleThe structure of myristoyl-CoA:protein N-myristoyltransferase.
[20]
PubMed ID11123906
JournalBiochemistry
Year2000
Volume39
Pages15807-16
AuthorsFarazi TA, Manchester JK, Gordon JI
TitleTransient-state kinetic analysis of Saccharomyces cerevisiae myristoylCoA:protein N-myristoyltransferase reveals that a step after chemical transformation is rate limiting.
[21]
PubMed ID10816442
JournalBiochem J
Year2000
Volume348
Pages459-63
AuthorsGunaratne RS, Sajid M, Ling IT, Tripathi R, Pachebat JA, Holder AA
TitleCharacterization of N-myristoyltransferase from Plasmodium falciparum.
[22]
PubMed ID11559351
JournalEur J Biochem
Year2001
Volume268
Pages4833-41
AuthorsMiura T, Klaus W, Ross A, Sakata K, Masubuchi M, Senn H
TitleProtein-bound conformation of a specific inhibitor against Candida albicans myristoyl-CoA:protein N-myristoyltransferase in the ternary complex with CaNmt and myristoyl-CoA by transferred NOE measurements.
[23]
PubMed ID11459642
JournalBioorg Med Chem Lett
Year2001
Volume11
Pages1833-7
AuthorsMasubuchi M, Kawasaki K, Ebiike H, Ikeda Y, Tsujii S, Sogabe S, Fujii T, Sakata K, Shiratori Y, Aoki Y, Ohtsuka T, Shimma N
TitleDesign and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 1.
[24]
PubMed ID11478885
JournalBiochemistry
Year2001
Volume40
Pages9177-86
AuthorsFarazi TA, Manchester JK, Waksman G, Gordon JI
TitlePre-steady-state kinetic studies of Saccharomyces cerevisiae myristoylCoA:protein N-myristoyltransferase mutants identify residues involved in catalysis.
[25]
PubMed ID11371195
JournalBiochemistry
Year2001
Volume40
Pages6335-43
AuthorsFarazi TA, Waksman G, Gordon JI
TitleStructures of Saccharomyces cerevisiae N-myristoyltransferase with bound myristoylCoA and peptide provide insights about substrate recognition and catalysis.
Related PDB1iic,1iid
[26]
PubMed ID11223516
JournalActa Crystallogr D Biol Crystallogr
Year2001
Volume57
Pages393-400
AuthorsFutterer K, Murray CL, Bhatnagar RS, Gokel GW, Gordon JI, Waksman G
TitleCrystallographic phasing of myristoyl-CoA-protein N-myristoyltransferase using an iodinated analog of myristoyl-CoA.
[27]
PubMed ID12401496
JournalChem Biol
Year2002
Volume9
Pages1119-28
AuthorsSogabe S, Masubuchi M, Sakata K, Fukami TA, Morikami K, Shiratori Y, Ebiike H, Kawasaki K, Aoki Y, Shimma N, D'Arcy A, Winkler FK, Banner DW, Ohtsuka T
TitleCrystal structures of Candida albicans N-myristoyltransferase with two distinct inhibitors.
Related PDB1iyk,1iyl

comments
According to the literature [16], [19], [24] & [25], the reaction of this enzyme proceeds as follows:
(1) Asn169 (of 2nmt) modulates the activity of a general base, the C-terminal carboxylate of Leu455, whereas an oxyanion hole, composed of the mainchain amide groups of Phe170 and Leu171, polarizes the transferred group, thioester carbonyl group of myristoyl-CoA, as a modulator.
(2) The modulated base, the C-terminal carboxylate of Leu455, activates the acceptor group, ammonium ion of Gly1 of substrate peptide, by deprotonating it.
(3) The activated (deprotonated) amine group of Gly1, which is stabilized by the sidechain of Asn169 and sidechain and mainchain carbonyl group of Thr205.
(4) The activated amine group makes a nucleophilic attack on the transferred carbonyl carbon, leading to a tetrahedral transition-state, which is stabilzed by the oxyanion hole of Phe170 and Leu171.
(5) Substrate-assisted proton donation to the leaving group, sulfur atom of CoA, by N6-amine of the CoA adenine completes the reaction.

createdupdated
2002-12-032009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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