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Information on EC 3.5.1.88 - peptide deformylase and Organism(s) Helicobacter pylori and UniProt Accession Q672W7
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3.5.1.88 peptide deformylaseIUBMB Comments
Requires Fe(II). Also requires at least a dipeptide for an efficient rate of reaction. N-terminal L-methionine is a prerequisite for activity but the enzyme has broad specificity at other positions. Differs in substrate specifity from EC 3.5.1.31 (formylmethionine deformylase).
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Word Map
- 3.5.1.88
- actinonin
- medicine
-
n-formylated
-
deformylation
- eubacteria
-
hydroxamic
- drug development
-
formyltransferase
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oxazolidinone
- catarrhalis
- linezolid
- moraxella
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hexxh
- biotechnology
- synthesis
- agriculture
- molecular biology
- analysis
The taxonomic range for the selected organisms is: Helicobacter pylori
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
peptide deformylase, hspdf, pdf-1, polypeptide deformylase, pdf1a, hppdf, pdf1b, pdf-2, atdef2, vp16 pdf, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
deformylase, peptide N-formylmethionine
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hydrolase, aminoacyl-transfer ribonucleate
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-
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PDF
Polypeptide deformylase
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PDF
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of amide bond
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-
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SYSTEMATIC NAME
IUBMB Comments
formyl-L-methionyl peptide amidohydrolase
Requires Fe(II). Also requires at least a dipeptide for an efficient rate of reaction. N-terminal L-methionine is a prerequisite for activity but the enzyme has broad specificity at other positions. Differs in substrate specifity from EC 3.5.1.31 (formylmethionine deformylase).
CAS REGISTRY NUMBER
COMMENTARY
369636-51-1
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37289-08-0
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9032-86-4
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9054-98-2
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
formyl-L-methionyl peptide + H2O
formate + L-methionyl peptide
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-
-
?
N-formyl-L-Met-L-Ala-L-Ser + H2O
formate + L-Met-L-Ala-L-Ser
activity assay
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-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
formyl-L-methionyl peptide + H2O
formate + L-methionyl peptide
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-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
Zn2+
Fe2+
bacterial PDF utilizes a Fe2+ ion as the catalytic metal ion. The Fe2+ ion in PDF is very unstable, and is rapidly and irreversibly oxidized to the Fe3+ ion through contact with atmospheric oxygen, resulting in an inactive enzyme. Addition of other divalent cations in vitro, such as Ni2+ or Co2+, result in better enzyme stability with very little loss of enzyme activity
additional information
the metal ion in the active site of PDF is tetrahedrally ligated and bound to the two histidines from the HEPhiDH motif, as well to a cysteine and a water molecule
Co2+
the activity of Co2+-containing enzyme is higher than the activity of Zn2+-containing enzyme
Zn2+
the activity of Co2+-containing enzyme is higher than the activity of Zn2+-containing enzyme
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(E)-N-phenethyl-3-(3,4-diacetoxyphenyl)acrylamide
IC50: 0.00125 mM
(2R)-N-[(1S)-1-(dimethylcarbamoyl)-2,2-dimethylpropyl]-2-[[formyl(hydroxy)amino]methyl]hexanamide
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i.e. BB-3497
(2R)-N-[(2S)-1-{4-[(2H-1,3-benzodioxol-5-yl)methyl]piperazin-1-yl}-3,3-dimethyl-1-oxobutan-2-yl]-2-(cyclopentylmethyl)-3-[formyl(hydroxy)amino]propanamide
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i.e. BB-83698
2-phenylethyl (2E)-3-(3,4-dihydroxyphenyl)prop-2-enoate
CAPE, does not chelate HpPDF and does not disrupt the metal-dependent catalysis
caffeic acid phenethyl ester
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CAPE, an active component of propolis, 75% inhibition at 0.01 mM, the competitive inhibitor blocks the substrate entrance, preventing substrate from approaching the active site, but CAPE does not have chelate interaction with HpPDF and does not disrupt the metal-dependent catalysis
N-[(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-6-[(9aS)-hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-2-methylpyrimidin-4-yl}hydrazinyl)-3-oxopropyl]-N-hydroxyformamide
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i.e. GSK1322322
tert-butyl 1-[(2R)-2-[2-(hydroxyamino)-2-oxoethyl]hexanoyl]-L-prolinate
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i.e. VRC-3375
actinonin
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95% inhibition at 0.01 mM, competitive, locates near the active site and plugs the substrate tunnel to prevent the substrate from accessing the catalytic site
additional information
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inhibition mechanism and kinetics, overview. No significant inhibition by caffeic acid, ferulic acid, chlorogenic acid, genistein, curcumin, naringenin, hesperitin, chrysin,apigenin, luteolin, kaempferol, myricetin, silibinin, and rutin at 0.01 mM
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additional information
different classes of PDF inhibitors, structures, and molecular modeling studies, overview
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00125
(E)-N-phenethyl-3-(3,4-diacetoxyphenyl)acrylamide
Helicobacter pylori
IC50: 0.00125 mM
0.00402
2-phenylethyl (2E)-3-(3,4-dihydroxyphenyl)prop-2-enoate
Helicobacter pylori
pH and temperature not specified in the publication
0.00402
caffeic acid phenethyl ester
Helicobacter pylori
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pH and temperature not specified in the publication
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.5 - 11
pH 6.5: about 55% of maximal activity, pH 11.0: about 90% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
40 - 60
40°C: about 50% of maximal activity, 60°C, about 70% of maximal activity
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
PDFs of all Gram-negative bacteria, some Gram-positive bacteria, and all eukaryotes fall systematically into type I class. The type II PDFs are found in Gram-positive bacteria (with low C+G content) and mycoplasma
metabolism
the PDF catalyzed deformylase reaction is part of the methionine molecular cycle, overview
physiological function
peptide deformylase (PDF) is a metalloenzyme and responsible for catalyzing the removal of the N-formyl group from N-terminal methionine following translation. Removal of the formyl group from polypeptide by PDF is a necessary activity for prokaryotic cell viability. This activity is not believed to be important in eukaryotic cells until recently, because nuclear encoded proteins are not N-formylated. But in eukaryotes, mitochondrial protein synthesis may also involve the formylation and deformylation process
additional information
proposed molecular catalytic mechanism of PDF, overview. The active site of PDF proteins contains three substrate binding pockets along with the metal binding site. These pockets are referred to as S1', S2', and S3' pockets and corresponding positions on substrate or inhibitors are referred to as P1', P2', and P3'
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
apo-HpPDF, HpPDF - N-trans-caffeoyltyramine complex, HpPDF - (E)-N-phenethyl-3-(3,4-diacetoxyphenyl)acrylamide complex
ligand-free enzyme, and complxed with inhibitors actinonin and caffeic acid phenethyl ester, hanging drop vapour diffusion method, condition screening, using 0.1 M HEPES, pH 7.5, 70% v/v MPD, mixing of 0.001 ml protein and reservoir solution each, and equilibration against 0.5 ml of reservoir solution, 17°C, X-ray diffraction structure determination and analysis at 1.66-1.70 A resolution
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
the enzyme is a drug target for antibacterial agents. Classification of PDF inhibitors, overview
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Han, C.; Wang, Q.; Dong, L.; Sun, H.; Peng, S.; Chen, J.; Yang, Y.; Yue, J.; Shen, X.; Jiang, H.
Molecular cloning and characterization of a new peptide deformylase from human pathogenic bacterium Helicobacter pylori
Biochem. Biophys. Res. Commun.
319
1292-1298
2004
Helicobacter pylori (Q672W7), Helicobacter pylori, Helicobacter pylori SS1 (Q672W7)
Cai, J.; Han, C.; Hu, T.; Zhang, J.; Wu, D.; Wang, F.; Liu, Y.; Ding, J.; Chen, K.; Yue, J.; Shen, X.; Jiang, H.
Peptide deformylase is a potential target for anti-Helicobacter pylori drugs: reverse docking, enzymatic assay, and X-ray crystallography validation
Protein Sci.
15
2071-2081
2006
Helicobacter pylori (Q672W7), Helicobacter pylori
Cui, K.; Lu, W.; Zhu, L.; Shen, X.; Huang, J.
Caffeic acid phenethyl ester (CAPE), an active component of propolis, inhibits Helicobacter pylori peptide deformylase activity
Biochem. Biophys. Res. Commun.
435
289-294
2013
Helicobacter pylori
Sangshetti, J.; Khan, F.; Shinde, D.
Peptide deformylase a new target in antibacterial, antimalarial and anticancer drug discovery
Curr. Med. Chem.
22
214-236
2015
Bacillus subtilis (P94462), Bacillus subtilis 168 (P94462), Escherichia coli (P0A6K3), Haemophilus influenzae (P44786), Haemophilus influenzae ATCC 51907 (P44786), Haemophilus influenzae DSM 11121 (P44786), Haemophilus influenzae KW20 (P44786), Haemophilus influenzae RD (P44786), Helicobacter pylori (P56419), Helicobacter pylori 26695 (P56419), Helicobacter pylori ATCC 700392 (P56419), Homo sapiens (Q9HBH1), Homo sapiens, Mycobacterium tuberculosis (P9WIJ3), Mycobacterium tuberculosis ATCC 25618 (P9WIJ3), Mycobacterium tuberculosis H37Rv (P9WIJ3), Plasmodium falciparum (Q8I372), Plasmodium falciparum isolate 3D7 (Q8I372), Staphylococcus aureus (P68826)
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