Acyl carrier protein

Acyl/peptidyl carrier protein
Streptomyces coelicolor actinorhodin polyketide synthase acyl carrier protein - PDB: 2AF8​
Identifiers
SymbolACP-like_sf
PfamPF00550
Pfam clanCL0314
InterProIPR036736
PROSITEPDOC00012
CATH1nq4
SCOP21nq4 / SCOPe / SUPFAM
Available protein structures:
PDB  IPR036736 PF00550 (ECOD; PDBsum)  
AlphaFold

The acyl carrier protein (ACP)[1], aryl carrier protein (ArCP), and the peptidyl carrier protein (PCP) are a family of protein cofactors that participate in fatty acid (acyl), polyketide (acyl and aryl), and nonribosomal peptide (peptidyl) biosynthesis. The growing molecule is bound to the A(r)/PCP via a thioester derived from the distal thiol of a 4'-phosphopantetheine (PPant) moiety.[2]

A(r)/PCPs are found in bacteria and eukaryotes (including humans) alike.[2] The E. coli version (EcacpP) is the best studied. In E. coli, the ACP is one of the most abundant cytosolic proteins at 0.25% of the total soluble protein (by molecule count). It is small, very acidic, and very soluble. EcacpP works as a cofactor in the synthesis of both long and short chain fatty acids in the bacterium. It interacts with fatty acid synthase proteins that "flips" the growing fatty acid chain out of the ACP's internal cavity and modifies it.[2] This kind of setup where the ACP exists as a free-floating protein is called Type II. An alternative is the Type I system, where a large protein contains several synthase domains as well as its own ACP domain. The ACP domain is pass around by the synthase domains to build a molecule.[3] Polyketide synthases and nonribosomal peptide synthetases interact with their carrier proteins in a similar way.[2] There is a similar distinction in how they are organized into type I and type II.[4][5]

Plant ACPs participate in the biosynthesis of fatty acids, exploited by humans in the form of vegetable oils.[6] Many polyketides and nonribosomal peptides produced with the help of A(r)/PCP are useful medications.[7]

Structure

The A/PCPs are small negatively charged α-helical bundle proteins with a high degree of structural and amino acid similarity. The structures of a number of acyl carrier proteins have been solved using various NMR and crystallography techniques.[8][9][10][11]

Biosynthesis

The A(r)/PCP is produced by the ribosome in the empty (apo) form. This form cannot function as a carrier protein. Only when acyl carrier protein synthase (ACPS) attaches the 4'-phosphopantetheine (PPant) prosthetic group to a serine residue is an active A(r)/PCP produced. The PPant group comes from coenzyme A.

Human proteins

Human genes containing a ACP domain include:[12]

  • AASDH
  • ALDH1L1
  • ALDH1L2
  • FASN
  • NDUFAB1 (mtACP)

Of these, mtACP is a "type II" ACP. All of these are processed by the human ACPS.[13][14]

References

  1. ^ Lawrence, Eleanor. "ACP". Henderson's Dictionary of Biological Terms (10th ed.). p. 1. ISBN 0-470-21446-5.
  2. ^ a b c d Cronan, John E. (2014). "The Chain-Flipping Mechanism of ACP (Acyl Carrier Protein)-Dependent enzymes Appears Universal". Biochemical Journal (Review article). 460 (2): 157–163. doi:10.1042/BJ20140239. PMID 24825445.
  3. ^ Buyachuihan, Lynn; Stegemann, Franziska; Grininger, Martin (22 January 2024). "How Acyl Carrier Proteins (ACPs) Direct Fatty Acid and Polyketide Biosynthesis". Angewandte Chemie International Edition. 63 (4) e202312476. Bibcode:2024ACIE...63E2476B. doi:10.1002/anie.202312476.
  4. ^ Jaremko, MJ; Davis, TD; Corpuz, JC; Burkart, MD (25 March 2020). "Type II non-ribosomal peptide synthetase proteins: structure, mechanism, and protein-protein interactions". Natural Product Reports. 37 (3): 355–379. doi:10.1039/c9np00047j. PMC 7101270. PMID 31593192.
  5. ^ Hertweck, Christian; Luzhetskyy, Andriy; Rebets, Yuri; Bechthold, Andreas (2007). "Type II polyketide synthases: gaining a deeper insight into enzymatic teamwork". Nat. Prod. Rep. 24 (1): 162–190. doi:10.1039/B507395M. PMID 17268612.
  6. ^ Yang, Xuezhen; Liu, Xiaoxue; Zhou, Yanchen; Zhang, Fan; Huang, Lan; Wang, Jun; Song, Jian; Qiu, Lijuan (January 2021). "New insights on the function of plant acyl carrier proteins from comparative and evolutionary analysis". Genomics. 113 (1): 1155–1165. doi:10.1016/j.ygeno.2020.11.015.
  7. ^ Walsh, Christopher T. (19 March 2004). "Polyketide and Nonribosomal Peptide Antibiotics: Modularity and Versatility". Science. 303 (5665): 1805–1810. Bibcode:2004Sci...303.1805W. doi:10.1126/science.1094318.
  8. ^ Roujeinikova A, Baldock C, Simon WJ, Gilroy J, Baker PJ, Stuitje AR, Rice DW, Slabas AR, Rafferty JB (June 2002). "X-ray crystallographic studies on butyryl-ACP reveal flexibility of the structure around a putative acyl chain binding site". Structure (Article). 10 (6). London, England: 825–35. doi:10.1016/s0969-2126(02)00775-x. PMID 12057197.
  9. ^ Crawford JM, Vagstad AL, Ehrlich KC, Udwary DW, Townsend CA (July 2008). "Acyl-carrier protein-phosphopantetheinyltransferase partnerships in fungal fatty acid synthases". ChemBioChem (Communication). 9 (10): 1559–63. doi:10.1002/cbic.200700659. PMC 3189688. PMID 18551496.
  10. ^ Volkman BF, Zhang Q, Debabov DV, Rivera E, Kresheck GC, Neuhaus FC (July 2001). "Biosynthesis of D-alanyl-lipoteichoic acid: the tertiary structure of apo-D-alanyl carrier protein". Biochemistry (Article). 40 (27): 7964–72. doi:10.1021/bi010355a. PMID 11434765.
  11. ^ Weber T, Baumgartner R, Renner C, Marahiel MA, Holak TA (April 2000). "Solution structure of PCP, a prototype for the peptidyl carrier domains of modular peptide synthetases". Structure (Research article). 8 (4): 407–18. doi:10.1016/s0969-2126(00)00120-9. PMID 10801488.
  12. ^ "InterPro".
  13. ^ Norden, Pieter R.; Wedan, Riley J.; Preston, Samuel E. J.; Canfield, Morgan; Graber, Naomi; Longenecker, Jacob Z.; Pentecost, Olivia A.; McLaughlin, Elizabeth; Hart, Madeleine L. (2024-05-10). "Mitochondrial Phosphopantetheinylation is Required for Oxidative Function". bioRxiv 10.1101/2024.05.09.592977.
  14. ^ Chen, Nan; Liu, Yuan; Li, Yuanpei; Wang, Chu (7 September 2020). "Chemical Proteomic Profiling of Protein 4′-Phosphopantetheinylation in Mammalian Cells". Angewandte Chemie International Edition. 59 (37): 16069–16075. doi:10.1002/anie.202004105. PMID 32537878.
This article is issued from Wikipedia. The text is available under Creative Commons Attribution-Share Alike 4.0 unless otherwise noted. Additional terms may apply for the media files.