11IZ

Crystal structure of HSC-HSC-AMS bound DesD, the desferrioxamine synthetase from the Streptomyces griseoflavus ferrimycin biosynthetic pathway

This is a non-PDB format compatible entry.

Summary for 11IZ

• Entry DOI: 10.2210/pdb11iz/pdb
• Descriptor: DesD, GLYCEROL, 5'-O-({4-[(5-{4-[(5-aminopentyl)(hydroxy)amino]-4-oxobutanamido}pentyl)(hydroxy)amino]-4-oxobutanoyl}sulfamoyl)adenosine, ... (7 entities in total)
• Functional Keywords: nis synthetase, nrps-independent siderophore synthetase, desferrioxamine synthetase, desd, ligase
• Biological source: Streptomyces griseoflavus
• Total number of polymer chains: 5
• Total formula weight: 353234.37

Authors

Patel, K.D.,Gulick, A.M. (deposition date: 2026-02-26, release date: 2026-08-26, Last modification date: 2026-09-02)

Primary citation

Merrick, C.E.,Patel, K.D.,Kalita, P.,Gulati, N.,Gulick, A.M.,Wencewicz, T.A.
Modular Inhibitor Approach to Map the Catalytic Trajectory of an Iterative Siderophore Synthetase, DesD.
Acs Bio Med Chem Au, 6:393-409, 2026

PubMed Abstract: Under iron limiting conditions, bacteria biosynthesize and secrete small molecule iron chelators, siderophores, to scavenge this essential metal. Siderophores are biosynthesized by nonribosomal peptide synthetases (NRPS) or NRPS independent siderophore (NIS) synthetases, the latter of which are significantly less studied. . utilizes an iterative NIS synthetase, DesD, to produce desferrioxamine type siderophores through dimerization, trimerization, and (in some cases) macrocyclization of monomers such as -hydroxy- -succinyl cadaverine (HSC) and -hydroxy- -acetyl cadaverine (HAC). Prior work has utilized an acyl-sulfamoyl adenosine (AMS) inhibitor of monomeric HSC (HSC-AMS) to interrogate the initial adenylation reaction of HSC. However, much is still unknown about how the enzyme active site accommodates substrates of varying sizes during further oligomerization reactions. To answer this question, AMS analogs of the monomer (HSC-AMS), dimer (HSC-HSC-AMS), and trimer (HSC-HSC-HSC-AMS) were chemically synthesized. Biochemical results from DesD reactions, IC assays, and isothermal titration calorimetry along with structural studies conducted via cocrystallization inform an updated mechanistic model for the iterative DesD catalytic cycle. The acyl adenylate motif in the growing substrate chain drives tight binding in the enzyme active site while the N-terminal HSC units dynamically sample conformations en route to terminating macrocyclization of the HSC-HSC-HSC trimer.

PubMed: 42630954
DOI: 10.1021/acsbiomedchemau.6c00078

Experimental method

X-RAY DIFFRACTION (2.47 Å)