Structural highlights
Function
[PAPA5_MYCTU] Catalyzes diesterification of phthiocerol and phthiodiolone with mycocerosic acids, the final step in the phthiocerol and phthiodiolone dimycocerosate esters (PDIM) synthesis. Can directly transfer the mycocerosate bound to the mycocerosic acid synthase (mas) onto the substrate alcohols. Is also able to catalyze acyl transfer using various nucleophiles as acceptors and several acyl-CoA thioesters as donors in vitro; preference is observed for saturated medium chain alcohols and long chain acyl-CoA thioesters.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Polyketide-associated protein A5 (PapA5) is an acyltransferase that is involved in production of phthiocerol and phthiodiolone dimycocerosate esters, a class of virulence-enhancing lipids produced by Mycobacterium tuberculosis. Structural analysis of PapA5 at 2.75-A resolution reveals a two-domain structure that shares unexpected similarity to structures of chloramphenicol acetyltransferase, dihydrolipoyl transacetylase, carnitine acetyltransferase, and VibH, a non-ribosomal peptide synthesis condensation enzyme. The PapA5 active site includes conserved histidine and aspartic acid residues that are critical to PapA5 acyltransferase activity. PapA5 catalyzes acyl transfer reactions on model substrates that contain long aliphatic carbon chains, and two hydrophobic channels were observed linking the PapA5 surface to the active site with properties consistent with these biochemical activities and substrate preferences. An additional alpha helix not observed in other acyltransferase structures blocks the putative entrance into the PapA5 active site, indicating that conformational changes may be associated with PapA5 activity. PapA5 represents the first structure solved for a protein involved in polyketide synthesis in Mycobacteria.
Crystal structure of PapA5, a phthiocerol dimycocerosyl transferase from Mycobacterium tuberculosis.,Buglino J, Onwueme KC, Ferreras JA, Quadri LE, Lima CD J Biol Chem. 2004 Jul 16;279(29):30634-42. Epub 2004 May 3. PMID:15123643[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Onwueme KC, Ferreras JA, Buglino J, Lima CD, Quadri LE. Mycobacterial polyketide-associated proteins are acyltransferases: proof of principle with Mycobacterium tuberculosis PapA5. Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4608-13. Epub 2004 Mar 18. PMID:15070765 doi:http://dx.doi.org/10.1073/pnas.0306928101
- ↑ Trivedi OA, Arora P, Vats A, Ansari MZ, Tickoo R, Sridharan V, Mohanty D, Gokhale RS. Dissecting the mechanism and assembly of a complex virulence mycobacterial lipid. Mol Cell. 2005 Mar 4;17(5):631-43. PMID:15749014 doi:http://dx.doi.org/S1097-2765(05)01086-5
- ↑ Buglino J, Onwueme KC, Ferreras JA, Quadri LE, Lima CD. Crystal structure of PapA5, a phthiocerol dimycocerosyl transferase from Mycobacterium tuberculosis. J Biol Chem. 2004 Jul 16;279(29):30634-42. Epub 2004 May 3. PMID:15123643 doi:10.1074/jbc.M404011200
