Energetic rationale for an unexpected and abrupt reversal of guanidinium chloride-induced unfolding of peptide deformylase.


Abstract

Peptide deformylase (PDF) catalyzes the removal of formyl group from the N-terminal methionine residues of nascent proteins in prokaryotes, and this enzyme is a high priority target for antibiotic design. In pursuit of delineating the structural-functional features of Escherichia coli PDF (EcPDF), we investigated the mechanistic pathway for the guanidinium chloride (GdmCl)-induced unfolding of the enzyme by monitoring the secondary structural changes via CD spectroscopy. The experimental data revealed that EcPDF is a highly stable enzyme, and it undergoes slow denaturation in the presence of varying concentrations of GdmCl. The most interesting aspect of these studies has been the abrupt reversal of the unfolding pathway at low to moderate concentrations of the denaturant, but not at high concentration. An energetic rationale for such an unprecedented feature in protein chemistry is offered. Study holds ProTherm entries: 23913 Extra Details: peptide deformylase; protein unfolding; denaturation; guanidinium chloride; CD spectroscopy

Submission Details

ID: 3tp74irP4

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:54 p.m.

Version: 1

Publication Details
Berg AK;Manokaran S;Eiler D;Kooren J;Mallik S;Srivastava DK,Protein Sci. (2008) Energetic rationale for an unexpected and abrupt reversal of guanidinium chloride-induced unfolding of peptide deformylase. PMID:18042674
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
1DEF 1997-04-21 PEPTIDE DEFORMYLASE CATALYTIC CORE (RESIDUES 1-147), NMR, 9 STRUCTURES
2KMN 2009-08-25 Solution structure of peptide deformylase complexed with actinonin
2DEF 1998-03-18 PEPTIDE DEFORMYLASE CATALYTIC CORE (RESIDUES 1-147), NMR, 20 STRUCTURES
1XEO 2005-03-29 1.3 High Resolution Crystals Structure of Cobalt- Peptide Deformylase Bound To Formate
2W3T 2009-12-15 1.69 Chloro complex of the Ni-Form of E.coli deformylase
2AI8 2005-09-06 1.7 E.coli Polypeptide Deformylase complexed with SB-485343
1G2A 2001-10-17 1.75 THE CRYSTAL STRUCTURE OF E.COLI PEPTIDE DEFORMYLASE COMPLEXED WITH ACTINONIN
1XEM 2005-03-29 1.76 High Resolution Crystal Structure of Escherichia coli Zinc- Peptide Deformylase bound to formate
1XEN 2005-03-29 1.85 High Resolution Crystal Structure of Escherichia coli Iron- Peptide Deformylase Bound To Formate
1BS4 1999-08-27 1.9 PEPTIDE DEFORMYLASE AS ZN2+ CONTAINING FORM (NATIVE) IN COMPLEX WITH INHIBITOR POLYETHYLENE GLYCOL
1ICJ 1999-03-23 1.9 PDF PROTEIN IS CRYSTALLIZED AS NI2+ CONTAINING FORM, COCRYSTALLIZED WITH INHIBITOR POLYETHYLENE GLYCOL (PEG)
1BSZ 1999-08-26 1.9 PEPTIDE DEFORMYLASE AS FE2+ CONTAINING FORM (NATIVE) IN COMPLEX WITH INHIBITOR POLYETHYLENE GLYCOL
2W3U 2009-12-15 1.96 formate complex of the Ni-Form of E.coli deformylase
4AL3 2012-04-04 1.98 peptide deformylase (Co-form) with mercaptoethanol
6IY7 2019-04-17 10.5 E. coli peptide deformylase crystal structure fitted into the cryo-EM density map of E. coli 70S ribosome in complex with peptide deformylase
6IZI 2019-04-17 11.8 Crystal structure of E. coli peptide deformylase and methionine aminopeptidase fitted into the cryo-EM density map of the complex
1BS6 1999-08-27 2.1 PEPTIDE DEFORMYLASE AS NI2+ CONTAINING FORM IN COMPLEX WITH TRIPEPTIDE MET-ALA-SER
1LRU 2002-07-24 2.1 Crystal Structure of E.coli Peptide Deformylase Complexed with Antibiotic Actinonin
1G27 2001-10-17 2.1 CRYSTAL STRUCTURE OF E.COLI POLYPEPTIDE DEFORMYLASE COMPLEXED WITH THE INHIBITOR BB-3497
3K6L 2009-11-10 2.15 The structure of E.coli peptide deformylase (PDF) in complex with peptidomimetic ligand BB2827
1BS8 1999-08-27 2.2 PEPTIDE DEFORMYLASE AS ZN2+ CONTAINING FORM IN COMPLEX WITH TRIPEPTIDE MET-ALA-SER
1BS5 1999-08-27 2.5 PEPTIDE DEFORMYLASE AS ZN2+ CONTAINING FORM
1BS7 1999-08-27 2.5 PEPTIDE DEFORMYLASE AS NI2+ CONTAINING FORM
4AL2 2012-04-04 2.6 peptide deformylase (Ni-form) with hydrosulfide
1DFF 1998-09-02 2.88 PEPTIDE DEFORMYLASE
1BSK 2000-04-15 3.0 ZINC DEFORMYLASE INHIBITOR COMPLEX FROM E.COLI
1BSJ 2000-04-15 3.0 COBALT DEFORMYLASE INHIBITOR COMPLEX FROM E.COLI
4V5B 2014-07-09 3.74 Structure of PDF binding helix in complex with the ribosome

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
92.0 Peptide deformylase B2VK93 DEF_ERWT9
90.9 Peptide deformylase A8GKG5 DEF_SERP5
92.7 Peptide deformylase A4WF95 DEF_ENT38
92.7 Peptide deformylase A7MPE9 DEF_CROS8
94.5 Peptide deformylase A6TEU0 DEF_KLEP7
95.7 Peptide deformylase B5XNC4 DEF_KLEP3
98.2 Peptide deformylase A8AQI1 DEF_CITK8
98.2 Peptide deformylase Q8Z1W9 DEF_SALTI
98.2 Peptide deformylase A9MN80 DEF_SALAR
98.8 Peptide deformylase Q8ZLM7 DEF_SALTY
98.8 Peptide deformylase B4TXB0 DEF_SALSV
98.8 Peptide deformylase B5BGV3 DEF_SALPK
98.8 Peptide deformylase A9N8B1 DEF_SALPB
98.8 Peptide deformylase Q5PIT8 DEF_SALPA
98.8 Peptide deformylase B4SUQ8 DEF_SALNS
98.8 Peptide deformylase B4TJX7 DEF_SALHS
98.8 Peptide deformylase B5RH49 DEF_SALG2
98.8 Peptide deformylase B5R1E3 DEF_SALEP
98.8 Peptide deformylase B5FJI2 DEF_SALDC
98.8 Peptide deformylase Q57J64 DEF_SALCH
98.8 Peptide deformylase B5F7R3 DEF_SALA4
99.4 Peptide deformylase Q3YWX3 DEF_SHISS
99.4 Peptide deformylase Q83PZ1 DEF_SHIFL
99.4 Peptide deformylase Q0T016 DEF_SHIF8
99.4 Peptide deformylase B2U2Q4 DEF_SHIB3
99.4 Peptide deformylase B1LGP3 DEF_ECOSM
99.4 Peptide deformylase B7NLK6 DEF_ECO7I
100.0 Peptide deformylase Q32B63 DEF_SHIDS
100.0 Peptide deformylase Q31VZ0 DEF_SHIBS
100.0 Peptide deformylase B7LRQ3 DEF_ESCF3
100.0 Peptide deformylase Q1R646 DEF_ECOUT
100.0 Peptide deformylase B6I200 DEF_ECOSE
100.0 Peptide deformylase B7NDQ8 DEF_ECOLU
100.0 Peptide deformylase P0A6K3 DEF_ECOLI
100.0 Peptide deformylase B1IQ13 DEF_ECOLC
100.0 Peptide deformylase P0A6K4 DEF_ECOL6
100.0 Peptide deformylase Q0TCH5 DEF_ECOL5
100.0 Peptide deformylase A1AGH8 DEF_ECOK1
100.0 Peptide deformylase A8A591 DEF_ECOHS
100.0 Peptide deformylase B1X6D9 DEF_ECODH
100.0 Peptide deformylase C4ZUE1 DEF_ECOBW
100.0 Peptide deformylase B7M0Z2 DEF_ECO8A
100.0 Peptide deformylase B7N171 DEF_ECO81
100.0 Peptide deformylase B5YT06 DEF_ECO5E
100.0 Peptide deformylase P0A6K5 DEF_ECO57
100.0 Peptide deformylase B7LHY3 DEF_ECO55
100.0 Peptide deformylase B7MCQ2 DEF_ECO45
100.0 Peptide deformylase B7UK10 DEF_ECO27
90.2 Peptide deformylase A1JRZ1 DEF_YERE8