6MFD

GphF GNAT-like decarboxylase in complex with isobutyryl-CoA

Summary for 6MFD

• Entry DOI: 10.2210/pdb6mfd/pdb
• Descriptor: GphF, ISOBUTYRYL-COENZYME A, ACETATE ION, ... (5 entities in total)
• Functional Keywords: decarboxylase, lyase
• Biological source: Cystobacter violaceus
• Total number of polymer chains: 2
• Total formula weight: 51248.17

Authors

Skiba, M.A.,Tran, C.L.,Smith, J.L. (deposition date: 2018-09-10, release date: 2019-09-18, Last modification date: 2023-10-11)

Primary citation

Skiba, M.A.,Tran, C.L.,Dan, Q.,Sikkema, A.P.,Klaver, Z.,Gerwick, W.H.,Sherman, D.H.,Smith, J.L.
Repurposing the GNAT Fold in the Initiation of Polyketide Biosynthesis.
Structure, 28:63-74.e4, 2020

PubMed Abstract: Natural product biosynthetic pathways are replete with enzymes repurposed for new catalytic functions. In some modular polyketide synthase (PKS) pathways, a GCN5-related N-acetyltransferase (GNAT)-like enzyme with an additional decarboxylation function initiates biosynthesis. Here, we probe two PKS GNAT-like domains for the dual activities of S-acyl transfer from coenzyme A (CoA) to an acyl carrier protein (ACP) and decarboxylation. The GphF and CurA GNAT-like domains selectively decarboxylate substrates that yield the anticipated pathway starter units. The GphF enzyme lacks detectable acyl transfer activity, and a crystal structure with an isobutyryl-CoA product analog reveals a partially occluded acyltransfer acceptor site. Further analysis indicates that the CurA GNAT-like domain also catalyzes only decarboxylation, and the initial acyl transfer is catalyzed by an unidentified enzyme. Thus, PKS GNAT-like domains are re-classified as GNAT-like decarboxylases. Two other decarboxylases, malonyl-CoA decarboxylase and EryM, reside on distant nodes of the superfamily, illustrating the adaptability of the GNAT fold.

PubMed: 31785925
DOI: 10.1016/j.str.2019.11.004

Experimental method

X-RAY DIFFRACTION (2.794 Å)