11iz

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

spinqualitylabelsall models 11iz, resolution 2.47Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 11iz is a 5 chain structure with sequence from Streptomyces griseoflavus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.47Å Ligands: A1C9F, DPO, GOL, MG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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. Streptomyces spp. utilizes an iterative NIS synthetase, DesD, to produce desferrioxamine type siderophores through dimerization, trimerization, and (in some cases) macrocyclization of monomers such as N (1)-hydroxy-N (1)-succinyl cadaverine (HSC) and N (1)-hydroxy-N (1)-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 in vitro DesD reactions, IC(50) 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. Modular Inhibitor Approach to Map the Catalytic Trajectory of an Iterative Siderophore Synthetase, DesD.,Merrick CE, Patel KD, Kalita P, Gulati N, Gulick AM, Wencewicz TA ACS Bio Med Chem Au. 2026 Jul 9;6(4):393-409. doi: , 10.1021/acsbiomedchemau.6c00078. eCollection 2026 Aug 19. PMID:42630954 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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