Peptide deformylase explained

In enzymology, a peptide deformylase is an enzyme that removes the formyl group from the N terminus of nascent polypeptide chains in eubacteria, mitochondria and chloroplasts.^[1]

Peptide deformylases are metaloenzymes monomers and bind a metal cofactor, typically Fe(II) or Zn, in an active site. Cofactor identity impacts catalytic efficiency.^[2]

There are two types of peptide deformylases, types I and II, which differ in structure mainly in the outer surface of the protein.

Human gene PDF (gene) possesses this activity.

Function

Peptide deformylase removes the formyl group from the N terminus of nascent polypeptides as they are synthesized by the ribosome.The function of peptide deformylase can be described by the following equation, where formyl-L-methionyl peptide and water react under the formation of formate and methionyl peptide:

H₂O + formyl-L-methionyl peptide

\rightleftharpoons methionyl peptide + formate

This reaction takes place on the surface of the ribosome, where the C-terminal alpha-helix of the peptide deformylase interacts with a grove between ribosomal proteins uL22 and bL32, and rRNA.^[3]

For its function this enzyme belongs to the family of hydrolases, those acting on carbon-nitrogen bonds other than peptide bonds, specifically in linear amides. The systematic name of this enzyme class is formyl-L-methionyl peptide amidohydrolase.

Structural studies

As of late 2007, 34 structures have been solved for this class of enzymes, with PDB accession codes,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, and .

See also

• Actinonin

Further reading

• Adams JM . On the release of the formyl group from nascent protein . Journal of Molecular Biology . 33 . 3 . 571–589 . May 1968 . 4973445 . 10.1016/0022-2836(68)90307-0 .
• Mazel D, Pochet S, Marlière P . Genetic characterization of polypeptide deformylase, a distinctive enzyme of eubacterial translation . The EMBO Journal . 13 . 4 . 914–923 . February 1994 . 8112305 . 394892 . 10.1002/j.1460-2075.1994.tb06335.x .
• Chan MK, Gong W, Rajagopalan PT, Hao B, Tsai CM, Pei D . Crystal structure of the Escherichia coli peptide deformylase . Biochemistry . 36 . 45 . 13904–13909 . November 1997 . 9374869 . 10.1021/bi9711543 .
• Becker A, Schlichting I, Kabsch W, Schultz S, Wagner AF . Structure of peptide deformylase and identification of the substrate binding site . The Journal of Biological Chemistry . 273 . 19 . 11413–11416 . May 1998 . 9565550 . 10.1074/jbc.273.19.11413 . free .
• Becker A, Schlichting I, Kabsch W, Groche D, Schultz S, Wagner AF . Iron center, substrate recognition and mechanism of peptide deformylase . Nature Structural Biology . 5 . 12 . 1053–1058 . December 1998 . 9846875 . 10.1038/4162 . 40528211 .
• Rajagopalan PT, Yu XC, Pei D . 1997 . Peptide deformylase: a new type of mononuclear iron protein . J. Am. Chem. Soc. . 119 . 12418 - 12419 . 10.1021/ja9734096 . 50 .
• Groche D, Becker A, Schlichting I, Kabsch W, Schultz S, Wagner AF . Isolation and crystallization of functionally competent Escherichia coli peptide deformylase forms containing either iron or nickel in the active site . Biochemical and Biophysical Research Communications . 246 . 2 . 342–346 . May 1998 . 9610360 . 10.1006/bbrc.1998.8616 .
• Rajagopalan PT, Grimme S, Pei D . Characterization of cobalt(II)-substituted peptide deformylase: function of the metal ion and the catalytic residue Glu-133 . Biochemistry . 39 . 4 . 779–790 . February 2000 . 10651644 . 10.1021/bi9919899 .
• Hu YJ, Wei Y, Zhou Y, Rajagopalan PT, Pei D . Determination of substrate specificity for peptide deformylase through the screening of a combinatorial peptide library . Biochemistry . 38 . 2 . 643–650 . January 1999 . 9888804 . 10.1021/bi9820412 .
• Ragusa S, Mouchet P, Lazennec C, Dive V, Meinnel T . Substrate recognition and selectivity of peptide deformylase. Similarities and differences with metzincins and thermolysin . Journal of Molecular Biology . 289 . 5 . 1445–1457 . June 1999 . 10373378 . 10.1006/jmbi.1999.2832 .
• Giglione C, Pierre M, Meinnel T . Peptide deformylase as a target for new generation, broad spectrum antimicrobial agents . Molecular Microbiology . 36 . 6 . 1197–1205 . June 2000 . 10931273 . 10.1046/j.1365-2958.2000.01908.x . 23289620 . free .
• Pei D . Peptide deformylase: a target for novel antibiotics? . Expert Opinion on Therapeutic Targets . 5 . 1 . 23–40 . February 2001 . 15992166 . 10.1517/14728222.5.1.23 . 11385977 .

Notes and References

1. Escobar-Alvarez S, Goldgur Y, Yang G, Ouerfelli O, Li Y, Scheinberg DA . Structure and activity of human mitochondrial peptide deformylase, a novel cancer target . Journal of Molecular Biology . 387 . 5 . 1211–1228 . April 2009 . 19236878 . 2782631 . 10.1016/j.jmb.2009.02.032 .
2. Becker A, Schlichting I, Kabsch W, Schultz S, Wagner AF . Structure of peptide deformylase and identification of the substrate binding site . The Journal of Biological Chemistry . 273 . 19 . 11413–11416 . May 1998 . 9565550 . 10.1074/jbc.273.19.11413 . free .
3. McGrath H, Černeková M, Kolář MH . Binding of the peptide deformylase on the ribosome surface modulates the exit tunnel interior . Biophysical Journal . 121 . 23 . 4443–4451 . December 2022 . 36335428 . 10.1016/j.bpj.2022.11.004 . 9748369 . 2022BpJ...121.4443M .