9E4U

TAD from Carmabin Biosynthetic Pathway in complex with NADH - Crystal Form 1

Summary for 9E4U

• Entry DOI: 10.2210/pdb9e4u/pdb
• Related: 9E4S
• Descriptor: Amino acid adenylation domain protein, 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE (3 entities in total)
• Functional Keywords: nad-binding, biosynthetic protein
• Biological source: Moorena producens 3L
• Total number of polymer chains: 2
• Total formula weight: 95944.32

Authors

Rankin, M.R.,Smith, J.L. (deposition date: 2024-10-25, release date: 2025-02-26, Last modification date: 2025-05-14)

Primary citation

Rankin, M.R.,Khare, D.,Gerwick, L.,Sherman, D.H.,Gerwick, W.H.,Smith, J.L.
Structure of a putative terminal amidation domain in natural product biosynthesis.
Structure, 33:935-, 2025

PubMed Abstract: Bacteria are rich sources of pharmaceutically valuable natural products, many crafted by modular polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS). PKS and NRPS systems typically contain a thioesterase (TE) to offload a linear or cyclized product from a carrier protein, but alternative chemistry is needed for products with a terminal amide. Several pathways with amidated products also possess an uncharacterized 400-amino acid terminal domain. We present the characterization and structure of this putative terminal amidation domain (TAD). TAD binds NAD with the nicotinamide near an invariant cysteine that is also accessible to an intermediate on a carrier protein, indicating a catalytic role. The TAD structure resembles cyanobacterial acyl-ACP reductase (AAR), which binds NADPH near an analogous catalytic cysteine. Bioinformatic analysis reveals that TADs are broadly distributed across bacterial phyla and often occur at the end of terminal NRPS modules, suggesting many amidated products may yet be discovered.

PubMed: 40086440
DOI: 10.1016/j.str.2025.02.005

Experimental method

X-RAY DIFFRACTION (2.23 Å)