EzCatDB: S00442

DB codeS00442
RLCP classification1.13.11100.561
CATH domainDomain 13.90.45.10Catalytic domain
E.C.3.5.1.88
CSA1bs4,1bsj
MACiEM0098


Enzyme Name
Swiss-protKEGG

P0A6K3
Protein namePeptide deformylasepeptide deformylase
SynonymsPDF
EC 3.5.1.88
Polypeptide deformylase


Swiss-prot:Accession NumberP0A6K3
Entry nameDEF_ECOLI
ActivityFormyl-L-methionyl peptide + H(2)O = formate + methionyl peptide.
SubunitMonomer.
Subcellular location
CofactorBinds 1 Fe(2+) ion per monomer.


CofactorsSubstratesProductsintermediates
KEGG-idC00023C11439C00001C00058C11440
CompoundFe2+Formyl-L-methionyl peptideH2OFormateMethionyl peptide
Typeheavy metalamide group,peptide/protein,sulfide groupH2Ocarboxyl grouppeptide/protein,sulfide group
1bs4AAnalogue:_ZNUnbound
UnboundUnboundUnbound
1bs4BAnalogue:_ZNUnbound
UnboundUnboundUnbound
1bs4CAnalogue:_ZNUnbound
UnboundUnboundUnbound
1bs5AAnalogue:_ZNUnbound
UnboundUnboundUnbound
1bs5BAnalogue:_ZNUnbound
UnboundUnboundUnbound
1bs5CAnalogue:_ZNUnbound
UnboundUnboundUnbound
1bs6AAnalogue:_NIUnbound
UnboundBound:MET-ALA-SERUnbound
1bs6BAnalogue:_NIUnbound
UnboundBound:MET-ALA-SERUnbound
1bs6CAnalogue:_NIUnbound
UnboundBound:MET-ALA-SERUnbound
1bs7AAnalogue:_NIUnbound
UnboundUnboundUnbound
1bs7BAnalogue:_NIUnbound
UnboundUnboundUnbound
1bs7CAnalogue:_NIUnbound
UnboundUnboundUnbound
1bs8AAnalogue:_ZNUnbound
UnboundBound:MET-ALA-SERUnbound
1bs8BAnalogue:_ZNUnbound
UnboundBound:MET-ALA-SERUnbound
1bs8CAnalogue:_ZNUnbound
UnboundBound:MET-ALA-SERUnbound
1bsjAAnalogue:_COUnbound
UnboundUnboundTransition-state-analogue:MLN
1bskAAnalogue:_ZNUnbound
UnboundUnboundTransition-state-analogue:MLN
1bszABound:_FEUnbound
UnboundUnboundUnbound
1bszBBound:_FEUnbound
UnboundUnboundUnbound
1bszCBound:_FEUnbound
UnboundUnboundUnbound
1defAAnalogue:_ZNUnbound
UnboundUnboundUnbound
1dffAAnalogue:_ZNUnbound
UnboundUnboundUnbound
1icjAAnalogue:_NIUnbound
UnboundUnboundUnbound
1icjBAnalogue:_NIUnbound
UnboundUnboundUnbound
1icjCAnalogue:_NIUnbound
UnboundUnboundUnbound
2defAAnalogue:_NIUnbound
UnboundUnboundUnbound

Active-site residues
pdbCatalytic residuesCofactor-binding residuesMain-chain involved in catalysis
1bs4AGLN   50;GLU  133
CYS   90;HIS  132;HIS  136(Fe binding)
LEU   91
1bs4BGLN  550;GLU  633
CYS  590;HIS  632;HIS  636(Fe binding)
LEU  591
1bs4CGLN 1050;GLU 1133
CYS 1090;HIS 1132;HIS 1136(Fe binding)
LEU 1091
1bs5AGLN   50;GLU  133
CYS   90;HIS  132;HIS  136(Fe binding)
LEU   91
1bs5BGLN  550;GLU  633
CYS  590;HIS  632;HIS  636(Fe binding)
LEU  591
1bs5CGLN 1050;GLU 1133
CYS 1090;HIS 1132;HIS 1136(Fe binding)
LEU 1091
1bs6AGLN   50;GLU  133
CYS   90;HIS  132;HIS  136(Fe binding)
LEU   91
1bs6BGLN  550;GLU  633
CYS  590;HIS  632;HIS  636(Fe binding)
LEU  591
1bs6CGLN 1050;GLU 1133
CYS 1090;HIS 1132;HIS 1136(Fe binding)
LEU 1091
1bs7AGLN   50;GLU  133
CYS   90;HIS  132;HIS  136(Fe binding)
LEU   91
1bs7BGLN  550;GLU  633
CYS  590;HIS  632;HIS  636(Fe binding)
LEU  591
1bs7CGLN 1050;GLU 1133
CYS 1090;HIS 1132;HIS 1136(Fe binding)
LEU 1091
1bs8AGLN   50;GLU  133
CYS   90;HIS  132;HIS  136(Fe binding)
LEU   91
1bs8BGLN  550;GLU  633
CYS  590;HIS  632;HIS  636(Fe binding)
LEU  591
1bs8CGLN 1050;GLU 1133
CYS 1090;HIS 1132;HIS 1136(Fe binding)
LEU 1091
1bsjAGLN   50;GLU  133
CYS   90;HIS  132;HIS  136(Fe binding)
LEU   91
1bskAGLN   50;GLU  133
CYS   90;HIS  132;HIS  136(Fe binding)
LEU   91
1bszAGLN   50;GLU  133
CYS   90;HIS  132;HIS  136(Fe binding)
LEU   91
1bszBGLN  550;GLU  633
CYS  590;HIS  632;HIS  636(Fe binding)
LEU  591
1bszCGLN 1050;GLU 1133
CYS 1090;HIS 1132;HIS 1136(Fe binding)
LEU 1091
1defAGLN   50;GLU  133
CYS   90;HIS  132;HIS  136(Fe binding)
LEU   91
1dffAGLN   50;GLU  133
CYS   90;HIS  132;HIS  136(Fe binding)
LEU   91
1icjAGLN   50;GLU  133
CYS   90;HIS  132;HIS  136(Fe binding)
LEU   91
1icjBGLN  550;GLU  633
CYS  590;HIS  632;HIS  636(Fe binding)
LEU  591
1icjCGLN 1050;GLU 1133
CYS 1090;HIS 1132;HIS 1136(Fe binding)
LEU 1091
2defAGLN   50;GLU  133
CYS   90;HIS  132;HIS  136(Fe binding)
LEU   91

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]p.180-181
[4]Fig.5, p.139082
[5]p.345-346
[6]p.11415-11416, Fig.5
[7]p.507-510
[10]Fig.3, p.1055-10562
[12]Fig.2, p.1454-1455
[13]Fig.6, p.4717-47182
[14]Fig.6, p.789-7902
[23]p.10567-10569

references
[1]
PubMed ID7490741
JournalJ Mol Biol
Year1995
Volume254
Pages175-83
AuthorsMeinnel T, Lazennec C, Blanquet S
TitleMapping of the active site zinc ligands of peptide deformylase.
[2]
CommentsNMR (solution structure of an active core domain)
Medline ID97002011
PubMed ID8845003
JournalJ Mol Biol
Year1996
Volume262
Pages375-86
AuthorsMeinnel T, Blanquet S, Dardel F
TitleA new subclass of the zinc metalloproteases superfamily revealed by the solution structure of peptide deformylase.
Related PDB1def
Related Swiss-protP0A6K3
[3]
PubMed ID9126850
JournalJ Mol Biol
Year1997
Volume267
Pages749-61
AuthorsMeinnel T, Lazennec C, Villoing S, Blanquet S
TitleStructure-function relationships within the peptide deformylase family. Evidence for a conserved architecture of the active site involving three conserved motifs and a metal ion.
[4]
CommentsX-ray crystallography (2.9 Angstroms)
Medline ID98042282
PubMed ID9374869
JournalBiochemistry
Year1997
Volume36
Pages13904-9
AuthorsChan MK, Gong W, Rajagopalan PT, Hao B, Tsai CM, Pei D
TitleCrystal structure of the Escherichia coli peptide deformylase.
Related PDB1dff
Related Swiss-protP0A6K3
[5]
Commentscofactor
Medline ID98273280
PubMed ID9610360
JournalBiochem Biophys Res Commun
Year1998
Volume246
Pages342-6
AuthorsGroche D, Becker A, Schlichting I, Kabsch W, Schultz S, Wagner AF
TitleIsolation and crystallization of functionally competent Escherichia coli peptide deformylase forms containing either iron or nickel in the active site.
Related Swiss-protP0A6K3
[6]
CommentsX-ray crystallography (1.9-2.5 Angstroms)
Medline ID98234316
PubMed ID9565550
JournalJ Biol Chem
Year1998
Volume273
Pages11413-6
AuthorsBecker A, Schlichting I, Kabsch W, Schultz S, Wagner AF
TitleStructure of peptide deformylase and identification of the substrate binding site.
Related PDB1bs7,1icj
Related Swiss-protP0A6K3
[7]
Commentsstructure by NMR
Medline ID98332750
PubMed ID9665852
JournalJ Mol Biol
Year1998
Volume280
Pages501-13
AuthorsDardel F, Ragusa S, Lazennec C, Blanquet S, Meinnel T
TitleSolution structure of nickel-peptide deformylase.
Related Swiss-protP0A6K3
[8]
PubMed ID9665853
JournalJ Mol Biol
Year1998
Volume280
Pages515-23
AuthorsRagusa S, Blanquet S, Meinnel T
TitleControl of peptide deformylase activity by metal cations.
[9]
PubMed ID9712848
JournalJ Biol Chem
Year1998
Volume273
Pages22305-10
AuthorsRajagopalan PT, Pei D
TitleOxygen-mediated inactivation of peptide deformylase.
[10]
CommentsX-ray crystallography (Fe2+, Ni2+ and Zn2+ forms, complex with the product)
Medline ID99061332
PubMed ID9846875
JournalNat Struct Biol
Year1998
Volume5
Pages1053-8
AuthorsBecker A, Schlichting I, Kabsch W, Groche D, Schultz S, Wagner AF
TitleIron center, substrate recognition and mechanism of peptide deformylase.
Related PDB1bs4,1bs5,1bs6,1bs8,1bsz
Related Swiss-protP0A6K3
[11]
PubMed ID9888804
JournalBiochemistry
Year1999
Volume38
Pages643-50
AuthorsHu YJ, Wei Y, Zhou Y, Rajagopalan PT, Pei D
TitleDetermination of substrate specificity for peptide deformylase through the screening of a combinatorial peptide library.
[12]
PubMed ID10373378
JournalJ Mol Biol
Year1999
Volume289
Pages1445-57
AuthorsRagusa S, Mouchet P, Lazennec C, Dive V, Meinnel T
TitleSubstrate recognition and selectivity of peptide deformylase. Similarities and differences with metzincins and thermolysin.
[13]
CommentsX-ray crystallography (bound to the transition-state analogue)
Medline ID99218079
PubMed ID10200158
JournalBiochemistry
Year1999
Volume38
Pages4712-9
AuthorsHao B, Gong W, Rajagopalan PT, Zhou Y, Pei D, Chan MK
TitleStructural basis for the design of antibiotics targeting peptide deformylase.
Related PDB1bsj,1bsk
Related Swiss-protP0A6K3
[14]
PubMed ID10651644
JournalBiochemistry
Year2000
Volume39
Pages779-90
AuthorsRajagopalan PT, Grimme S, Pei D
TitleCharacterization of cobalt(II)-substituted peptide deformylase: function of the metal ion and the catalytic residue Glu-133.
[15]
PubMed ID11429456
JournalMicrobiology
Year2001
Volume147
Pages1783-91
AuthorsHaas M, Beyer D, Gahlmann R, Freiberg C
TitleYkrB is the main peptide deformylase in Bacillus subtilis, a eubacterium containing two functional peptide deformylases.
[16]
PubMed ID11733990
JournalJ Mol Biol
Year2001
Volume314
Pages695-708
AuthorsSerero A, Giglione C, Meinnel T
TitleDistinctive features of the two classes of eukaryotic peptide deformylases.
[17]
PubMed ID11747293
JournalArch Biochem Biophys
Year2001
Volume396
Pages162-70
AuthorsBracchi-Ricard V, Nguyen KT, Zhou Y, Rajagopalan PT, Chakrabarti D, Pei D
TitleCharacterization of an eukaryotic peptide deformylase from Plasmodium falciparum.
[18]
PubMed ID11800612
JournalInorg Chem
Year2002
Volume41
Pages239-48
AuthorsChang S, Karambelkar VV, Sommer RD, Rheingold AL, Goldberg DP
TitleNew monomeric cobalt(II) and zinc(II) complexes of a mixed N,S(alkylthiolate) ligand: model complexes of (His)(His)(Cys) metalloprotein active sites.
[19]
PubMed ID12005434
JournalStructure (Camb)
Year2002
Volume10
Pages357-67
AuthorsKumar A, Nguyen KT, Srivathsan S, Ornstein B, Turley S, Hirsh I, Pei D, Hol WG
TitleCrystals of peptide deformylase from Plasmodium falciparum reveal critical characteristics of the active site for drug design.
[20]
PubMed ID12048187
JournalJ Biol Chem
Year2002
Volume277
Pages31163-71
AuthorsBaldwin ET, Harris MS, Yem AW, Wolfe CL, Vosters AF, Curry KA, Murray RW, Bock JH, Marshall VP, Cialdella JI, Merchant MH, Choi G, Deibel MR Jr
TitleCrystal structure of type II peptide deformylase from Staphylococcus aureus.
[21]
PubMed ID12126617
JournalJ Mol Biol
Year2002
Volume320
Pages951-62
AuthorsGuilloteau JP, Mathieu M, Giglione C, Blanc V, Dupuy A, Chevrier M, Gil P, Famechon A, Meinnel T, Mikol V
TitleThe crystal structures of four peptide deformylases bound to the antibiotic actinonin reveal two distinct types: a platform for the structure-based design of antibacterial agents.
[22]
PubMed ID12127977
JournalBiochem Biophys Res Commun
Year2002
Volume295
Pages884-9
AuthorsLi Y, Chen Z, Gong W
TitleEnzymatic properties of a new peptide deformylase from pathogenic bacterium Leptospira interrogans.
[23]
PubMed ID12173943
JournalBiochemistry
Year2002
Volume41
Pages10563-9
AuthorsDeng H, Callender R, Zhu J, Nguyen KT, Pei D
TitleDetermination of the ionization state and catalytic function of Glu-133 in peptide deformylase by difference FTIR spectroscopy.
[24]
PubMed ID12240093
JournalChem Commun (Camb)
Year2001
Volume(22)
Pages2396-7
AuthorsChang SC, Sommer RD, Rheingold AL, Goldberg DP
TitleA model complex of a possible intermediate in the mechanism of action of peptide deformylase: first example of an (N2S)zinc(II)-formate complex.
[25]
PubMed ID12488004
JournalBiophys Chem
Year2002
Volume101-102
Pages239-47
AuthorsMadison V, Duca J, Bennett F, Bohanon S, Cooper A, Chu M, Desai J, Girijavallabhan V, Hare R, Hruza A, Hendrata S, Huang Y, Kravec C, Malcolm B, McCormick J, Miesel L, Ramanathan L, Reichert P, Saksena A, Wang J, Weber PC, Zhu H, Fischmann T
TitleBinding affinities and geometries of various metal ligands in peptide deformylase inhibitors.
[26]
PubMed ID12823970
JournalJ Mol Biol
Year2003
Volume330
Pages309-21
AuthorsKreusch A, Spraggon G, Lee CC, Klock H, McMullan D, Ng K, Shin T, Vincent J, Warner I, Ericson C, Lesley SA
TitleStructure analysis of peptide deformylases from Streptococcus pneumoniae, Staphylococcus aureus, Thermotoga maritima and Pseudomonas aeruginosa: snapshots of the oxygen sensitivity of peptide deformylase.
[27]
PubMed ID12924944
JournalBiochemistry
Year2003
Volume42
Pages9952-8
AuthorsNguyen KT, Hu X, Colton C, Chakrabarti R, Zhu MX, Pei D
TitleCharacterization of a human peptide deformylase: implications for antibacterial drug design.
[28]
PubMed ID12971750
JournalInorg Chem
Year2003
Volume42
Pages5825-36
AuthorsDiTargiani RC, Chang S, Salter MH Jr, Hancock RD, Goldberg DP
TitleHydrolysis of 4-Nitrophenyl Acetate by a (N(2)S(thiolate))zinc Hydroxide Complex: A Model of the Catalytically Active Intermediate for the Zinc Form of Peptide Deformylase.

comments
This enzyme belongs to the polypeptide deformylase family.
According to the literature [5] & [6], this enzyme is a Fe2+ enzyme instead of a zinc metalloprotease, showing that the zinc form is inactive.
There are a few proposed mechanism for the catalysis, raising some questions as follows:
(1) The number of the coordination of the metal involved in the catalysis, four or five: Whether the formyl carbonyl group is coordinated to the metal is still controversial.
(2) The function of Glu133: Whether this residue functions as a general base to activate the catalytic water molecule remains unclear.
As for the question (1), the papers [4] & [10] propsed a five-coordinated metal center, in which the formyl carbonyl group is coordinated to the catalytic metal, whilst the others [13] & [14] suggested a four-coordinated metal one. According to the paper [10], the state of the carbonyl carbon changes, accompanied by a transition from the four-coordinated to the five-coordinated metal center, this transition being strongly inhibited in the case of zinc form due to the tighter binding of this metal ion as compared with Fe2+ or Ni2+.
As for the question (2), in the early work on the catalysis [4], [12] & [13], Glu133 had been considered to play a dual role as a general base to activate the catalytic water, then as a general acid to protonate the leaving amide ion. However, more recently, some papers [14] & [23] suggested that Glu133 is not so critical as the general base during the catalysis, only functioning as a general acid donating the proton to the leaving group.
In any case, according to the above papers, the common feature of the catalytic mechanism is as follows:
(1) The negative charge of the carbonyl oxygen of the formyl group is stabilized by the amide of Leu91 and the sidechain of Gln50.
(2) The water or hydroxide bound to the catalytic metal (Fe2+, Ni2+ or Co2+) makes a nucleophilic attack on the carbonyl carbon that leads to a transition state (giving a four-coordinated or a five-coordinated metal center).
(3) Glu133 protonates the leaving amide group for the cleavage.

createdupdated
2003-01-272009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
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 2010)
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)

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