DB code: D00413

RLCP classification 3.1147.47600.180 : Transfer
CATH domain 3.40.630.30 : Aminopeptidase Catalytic domain
3.40.630.30 : Aminopeptidase
E.C. 2.3.1.97
CSA 2nmt
M-CSA 2nmt
MACiE

CATH domain Related DB codes (homologues)
3.40.630.30 : Aminopeptidase M00165 S00409 S00410 T00034

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P30418 Glycylpeptide N-tetradecanoyltransferase
EC 2.3.1.97
Myristoyl-CoA:protein N-myristoyltransferase
NMT
Peptide N-myristoyltransferase
XP_722713.1 (Protein)
XM_717620.1 (DNA/RNA sequence)
XP_722859.1 (Protein)
XM_717766.1 (DNA/RNA sequence)
PF01233 (NMT)
PF02799 (NMT_C)
[Graphical View]
P14743 Glycylpeptide N-tetradecanoyltransferase
EC 2.3.1.97
Cell division control protein 72
Myristoyl-CoA:protein N-myristoyltransferase
NMT
Peptide N-myristoyltransferase
NP_013296.1 (Protein)
NM_001182082.1 (DNA/RNA sequence)
PF01233 (NMT)
PF02799 (NMT_C)
[Graphical View]

KEGG enzyme name
glycylpeptide N-tetradecanoyltransferase
peptide N-myristoyltransferase
myristoyl-CoA-protein N-myristoyltransferase
myristoyl-coenzyme A:protein N-myristoyl transferase
myristoylating enzymes
protein N-myristoyltransferase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P14743 NMT_YEAST Tetradecanoyl-CoA + glycylpeptide = CoA + N- tetradecanoylglycylpeptide. Monomer. Cytoplasm.
P30418 NMT_CANAL Tetradecanoyl-CoA + glycylpeptide = CoA + N- tetradecanoylglycylpeptide. Monomer. Cytoplasm.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C02593 C02038 C00010 C03881
E.C.
Compound Tetradecanoyl-CoA Glycylpeptide CoA N-Tetradecanoylglycylpeptide
Type amine group,carbohydrate,lipid,nucleotide ,peptide/protein,sulfide group amine group,carboxyl group,peptide/protein amine group,carbohydrate,nucleotide ,peptide/protein,sulfhydryl group carboxyl group,lipid,peptide/protein
ChEBI 15532
15346
PubChem 11966124
65113
6816
87642
1iykA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:MYA Unbound Unbound Unbound
1iykB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:MYA Unbound Unbound Unbound
1iylA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1iylB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1iylC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1iylD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1nmtA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1nmtB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1nmtC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1iicA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:MYA Unbound Unbound Unbound
1iicB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:MYA Unbound Unbound Unbound
1iidA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:NHM Unbound Unbound Unbound
2nmtA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:NHM Unbound Unbound Unbound
1iykA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:MIM Unbound Unbound
1iykB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:MIM Unbound Unbound
1iylA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:R64 Unbound Unbound
1iylB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:R64 Unbound Unbound
1iylC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:R64 Unbound Unbound
1iylD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:R64 Unbound Unbound
1nmtA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1nmtB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1nmtC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1iicA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1iicB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1iidA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:GLY-LEU-TYR-ALA-SER-LYS-LEU-ALA (chain O) Unbound Unbound
2nmtA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:MIM Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [16], [12]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1iykA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 175;THR 211 PHE 176;LEU 177;THR 211
1iykB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 175;THR 211 PHE 176;LEU 177;THR 211
1iylA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 175;THR 211 PHE 176;LEU 177;THR 211
1iylB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 175;THR 211 PHE 176;LEU 177;THR 211
1iylC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 175;THR 211 PHE 176;LEU 177;THR 211
1iylD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 175;THR 211 PHE 176;LEU 177;THR 211
1nmtA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 175;THR 211 PHE 176;LEU 177;THR 211
1nmtB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 175;THR 211 PHE 176;LEU 177;THR 211
1nmtC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 175;THR 211 PHE 176;LEU 177;THR 211
1iicA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 169;THR 205 PHE 170;LEU 171;THR 205
1iicB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 169;THR 205 PHE 170;LEU 171;THR 205
1iidA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 169;THR 205 PHE 170;LEU 171;THR 205
2nmtA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 169;THR 205 PHE 170;LEU 171;THR 205
1iykA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LEU 451
1iykB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LEU 451
1iylA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LEU 451
1iylB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LEU 451
1iylC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LEU 451
1iylD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LEU 451
1nmtA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LEU 451
1nmtB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LEU 451
1nmtC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LEU 451
1iicA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LEU 455
1iicB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LEU 455
1iidA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LEU 455
2nmtA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LEU 455

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[12]
Fig.4, p.30891-30892 4
[16]
Fig.5b, p.1094 3
[17]
p.216-217
[18]
Fig.4, p.14933-14934 3
[19]
Fig.6, p.169-170 3
[20]
p.15814
[25]
Fig.3, Fig.4, p.6341-6342 3

References
[1]
Resource
Comments MUTAGENESIS OF GLY-451
Medline ID
PubMed ID 2045414
Journal J Cell Biol
Year 1991
Volume 113
Pages 1313-30
Authors Duronio RJ, Rudnick DA, Johnson RL, Johnson DR, Gordon JI
Title Myristic acid auxotrophy caused by mutation of S. cerevisiae myristoyl-CoA:protein N-myristoyltransferase.
Related PDB
Related UniProtKB P14743
[2]
Resource
Comments
Medline ID
PubMed ID 2033063
Journal J Biol Chem
Year 1991
Volume 266
Pages 9732-9
Authors Rudnick DA, McWherter CA, Rocque WJ, Lennon PJ, Getman DP, Gordon JI
Title Kinetic and structural evidence for a sequential ordered Bi Bi mechanism of catalysis by Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 1999191
Journal Eur J Biochem
Year 1991
Volume 195
Pages 699-705
Authors Wagner AP, Retey J
Title Synthesis of myristoyl-carba(dethia)-coenzyme A and S-(3-oxohexadecyl)-coenzyme A, two potent inhibitors of myristoyl-CoA:protein N-myristoyltransferase.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 1559967
Journal J Biol Chem
Year 1992
Volume 267
Pages 7224-39
Authors Devadas B, Lu T, Katoh A, Kishore NS, Wade AC, Mehta PP, Rudnick DA, Bryant ML, Adams SP, Li Q, et al
Title Substrate 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.
Related PDB
Related UniProtKB
[5]
Resource
Comments CHARACTERIZATION
Medline ID
PubMed ID 8430078
Journal Proc Natl Acad Sci U S A
Year 1993
Volume 90
Pages 1087-91
Authors Rudnick DA, Rocque WJ, McWherter CA, Toth MV, Jackson-Machelski E, Gordon JI
Title Use 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 PDB
Related UniProtKB P14743
[6]
Resource
Comments MUTAGENESIS OF LEU-99
Medline ID
PubMed ID 8416952
Journal J Biol Chem
Year 1993
Volume 268
Pages 483-94
Authors Johnson DR, Duronio RJ, Langner CA, Rudnick DA, Gordon JI
Title Genetic and biochemical studies of a mutant Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase, nmt72pLeu99-->Pro, that produces temperature-sensitive myristic acid auxotrophy.
Related PDB
Related UniProtKB P14743
[7]
Resource
Comments
Medline ID
PubMed ID 8486723
Journal J Biol Chem
Year 1993
Volume 268
Pages 9964-71
Authors Rocque WJ, McWherter CA, Wood DC, Gordon JI
Title A comparative analysis of the kinetic mechanism and peptide substrate specificity of human and Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 8322618
Journal Adv Enzymol Relat Areas Mol Biol
Year 1993
Volume 67
Pages 375-430
Authors Rudnick DA, McWherter CA, Gokel GW, Gordon JI
Title MyristoylCoA:protein N-myristoyltransferase.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 8169796
Journal J Pharm Sci
Year 1994
Volume 83
Pages 233-8
Authors Zheng GQ, Hu X, Cassady JM, Paige LA, Geahlen RL
Title Synthesis of myristoyl CoA analogues and myristoyl peptides as inhibitors of myristoyl CoA:protein N-myristoyltransferase.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 8157630
Journal J Biol Chem
Year 1994
Volume 269
Pages 11045-53
Authors Bhatnagar RS, Jackson-Machelski E, McWherter CA, Gordon JI
Title Isothermal titration calorimetric studies of Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase. Determinants of binding energy and catalytic discrimination among acyl-CoA and peptide ligands.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 8300631
Journal J Biol Chem
Year 1994
Volume 269
Pages 2996-3009
Authors Lodge JK, Johnson RL, Weinberg RA, Gordon JI
Title Comparison of myristoyl-CoA:protein N-myristoyltransferases from three pathogenic fungi: Cryptococcus neoformans, Histoplasma capsulatum, and Candida albicans.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 7983020
Journal J Biol Chem
Year 1994
Volume 269
Pages 30888-92
Authors Peseckis SM, Resh MD
Title Fatty acyl transfer by human N-myristyl transferase is dependent upon conserved cysteine and histidine residues.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 9154965
Journal J Med Chem
Year 1997
Volume 40
Pages 1422-38
Authors Nagarajan SR, Devadas B, Zupec ME, Freeman SK, Brown DL, Lu HF, Mehta PP, Kishore NS, McWherter CA, Getman DP, Gordon JI, Sikorski JA
Title Conformationally 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.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 9044045
Journal J Cell Sci
Year 1997
Volume 110
Pages 149-56
Authors Ntwasa M, Egerton M, Gay NJ
Title Sequence and expression of Drosophila myristoyl-CoA: protein N-myristoyl transferase: evidence for proteolytic processing and membrane localisation.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 9184150
Journal Biochemistry
Year 1997
Volume 36
Pages 6700-8
Authors Bhatnagar RS, Schall OF, Jackson-Machelski E, Sikorski JA, Devadas B, Gokel GW, Gordon JI
Title Titration calorimetric analysis of AcylCoA recognition by myristoylCoA:protein N-myristoyltransferase.
Related PDB
Related UniProtKB
[16]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS)
Medline ID
PubMed ID 9846880
Journal Nat Struct Biol
Year 1998
Volume 5
Pages 1091-7
Authors Bhatnagar RS, Futterer K, Farazi TA, Korolev S, Murray CL, Jackson-Machelski E, Gokel GW, Gordon JI, Waksman G
Title Structure of N-myristoyltransferase with bound myristoylCoA and peptide substrate analogs.
Related PDB 2nmt
Related UniProtKB P14743
[17]
Resource
Comments
Medline ID
PubMed ID 9501915
Journal Nat Struct Biol
Year 1998
Volume 5
Pages 213-21
Authors Weston 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
Title Crystal structure of the anti-fungal target N-myristoyl transferase.
Related PDB 1nmt
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 9778369
Journal Biochemistry
Year 1998
Volume 37
Pages 14928-36
Authors Raju RV, Datla RS, Warrington RC, Sharma RK
Title Effects of L-histidine and its structural analogues on human N-myristoyltransferase activity and importance of EEVEH amino acid sequence for enzyme activity.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 10570244
Journal Biochim Biophys Acta
Year 1999
Volume 1441
Pages 162-72
Authors Bhatnagar RS, Futterer K, Waksman G, Gordon JIThe structure of myristoyl-CoA:protein N-myristoyltransferase
Title The structure of myristoyl-CoA:protein N-myristoyltransferase.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 11123906
Journal Biochemistry
Year 2000
Volume 39
Pages 15807-16
Authors Farazi TA, Manchester JK, Gordon JI
Title Transient-state kinetic analysis of Saccharomyces cerevisiae myristoylCoA:protein N-myristoyltransferase reveals that a step after chemical transformation is rate limiting.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 10816442
Journal Biochem J
Year 2000
Volume 348
Pages 459-63
Authors Gunaratne RS, Sajid M, Ling IT, Tripathi R, Pachebat JA, Holder AA
Title Characterization of N-myristoyltransferase from Plasmodium falciparum.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 11559351
Journal Eur J Biochem
Year 2001
Volume 268
Pages 4833-41
Authors Miura T, Klaus W, Ross A, Sakata K, Masubuchi M, Senn H
Title Protein-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.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 11459642
Journal Bioorg Med Chem Lett
Year 2001
Volume 11
Pages 1833-7
Authors Masubuchi M, Kawasaki K, Ebiike H, Ikeda Y, Tsujii S, Sogabe S, Fujii T, Sakata K, Shiratori Y, Aoki Y, Ohtsuka T, Shimma N
Title Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 1.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 11478885
Journal Biochemistry
Year 2001
Volume 40
Pages 9177-86
Authors Farazi TA, Manchester JK, Waksman G, Gordon JI
Title Pre-steady-state kinetic studies of Saccharomyces cerevisiae myristoylCoA:protein N-myristoyltransferase mutants identify residues involved in catalysis.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 11371195
Journal Biochemistry
Year 2001
Volume 40
Pages 6335-43
Authors Farazi TA, Waksman G, Gordon JI
Title Structures of Saccharomyces cerevisiae N-myristoyltransferase with bound myristoylCoA and peptide provide insights about substrate recognition and catalysis.
Related PDB 1iic 1iid
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 11223516
Journal Acta Crystallogr D Biol Crystallogr
Year 2001
Volume 57
Pages 393-400
Authors Futterer K, Murray CL, Bhatnagar RS, Gokel GW, Gordon JI, Waksman G
Title Crystallographic phasing of myristoyl-CoA-protein N-myristoyltransferase using an iodinated analog of myristoyl-CoA.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID 12401496
Journal Chem Biol
Year 2002
Volume 9
Pages 1119-28
Authors Sogabe 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
Title Crystal structures of Candida albicans N-myristoyltransferase with two distinct inhibitors.
Related PDB 1iyk 1iyl
Related UniProtKB

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.

Created Updated
2002-12-03 2009-02-26