Structural highlights
Function
[ACYLT_MYCS2] Catalyzes the acylation to the position 6 of the alpha-1,2-linked mannose residue of the phosphatidyl-myo-inositol dimannoside (PIM2) or monomannoside (PIM1).[1]
Publication Abstract from PubMed
The biosynthesis of phospholipids and glycolipids are critical pathways for virtually all cell membranes. PatA is an essential membrane associated acyltransferase involved in the biosynthesis of mycobacterial phosphatidyl-myo-inositol mannosides (PIMs). The enzyme transfers a palmitoyl moiety from palmitoyl-CoA to the 6-position of the mannose ring linked to 2-position of inositol in PIM1/PIM2. We report here the crystal structures of PatA from Mycobacterium smegmatis in the presence of its naturally occurring acyl donor palmitate and a nonhydrolyzable palmitoyl-CoA analog. The structures reveal an alpha/beta architecture, with the acyl chain deeply buried into a hydrophobic pocket that runs perpendicular to a long groove where the active site is located. Enzyme catalysis is mediated by an unprecedented charge relay system, which markedly diverges from the canonical HX4D motif. Our studies establish the mechanistic basis of substrate/membrane recognition and catalysis for an important family of acyltransferases, providing exciting possibilities for inhibitor design.
Structural basis for selective recognition of acyl chains by the membrane-associated acyltransferase PatA.,Albesa-Jove D, Svetlikova Z, Tersa M, Sancho-Vaello E, Carreras-Gonzalez A, Bonnet P, Arrasate P, Eguskiza A, Angala SK, Cifuente JO, Kordulakova J, Jackson M, Mikusova K, Guerin ME Nat Commun. 2016 Mar 11;7:10906. doi: 10.1038/ncomms10906. PMID:26965057[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kordulakova J, Gilleron M, Puzo G, Brennan PJ, Gicquel B, Mikusova K, Jackson M. Identification of the required acyltransferase step in the biosynthesis of the phosphatidylinositol mannosides of mycobacterium species. J Biol Chem. 2003 Sep 19;278(38):36285-95. Epub 2003 Jul 8. PMID:12851411 doi:http://dx.doi.org/10.1074/jbc.M303639200
- ↑ Albesa-Jove D, Svetlikova Z, Tersa M, Sancho-Vaello E, Carreras-Gonzalez A, Bonnet P, Arrasate P, Eguskiza A, Angala SK, Cifuente JO, Kordulakova J, Jackson M, Mikusova K, Guerin ME. Structural basis for selective recognition of acyl chains by the membrane-associated acyltransferase PatA. Nat Commun. 2016 Mar 11;7:10906. doi: 10.1038/ncomms10906. PMID:26965057 doi:http://dx.doi.org/10.1038/ncomms10906
