7VZA

The crystal structure of Non-hydrolyzing UDPGlcNAc 2-epimerase in complex with UDP

Summary for 7VZA

• Entry DOI: 10.2210/pdb7vza/pdb
• Descriptor: Putative UDP-N-acetylglucosamine 2-epimerase, URIDINE-5'-DIPHOSPHATE, SODIUM ION, ... (4 entities in total)
• Functional Keywords: epimerase, udp-sugars, isomerase
• Biological source: Streptomyces kasugaensis
• Total number of polymer chains: 8
• Total formula weight: 333083.02

Authors

Li, T.L.,Rattinam, R. (deposition date: 2021-11-15, release date: 2022-11-16, Last modification date: 2023-11-29)

Primary citation

Rattinam, R.,Basha, R.S.,Wang, Y.L.,Wang, Z.C.,Hsu, N.S.,Lin, K.H.,Zadeh, S.M.,Adhikari, K.,Lin, J.P.,Li, T.L.
KasQ an Epimerase Primes the Biosynthesis of Aminoglycoside Antibiotic Kasugamycin and KasF/H Acetyltransferases Inactivate Its Activity.
Biomedicines, 10:-, 2022

PubMed Abstract: Kasugamycin (KSM), an aminoglycoside antibiotic, is composed of three chemical moieties: D--inositol, kasugamine and glycine imine. Despite being discovered more than 50 years ago, the biosynthetic pathway of KSM remains an unresolved puzzle. Here we report a structural and functional analysis for an epimerase, KasQ, that primes KSM biosynthesis rather than the previously proposed KasF/H, which instead acts as an acetyltransferase, inactivating KSM. Our biochemical and biophysical analysis determined that KasQ converts UDP-GlcNAc to UDP-ManNAc as the initial step in the biosynthetic pathway. The isotope-feeding study further confirmed that C, N-glucosamine/UDP-GlcNH rather than glucose/UDP-Glc serves as the direct precursor for the formation of KSM. Both KasF and KasH were proposed, respectively, converting UDP-GlcNH and KSM to UDP-GlcNAc and 2-N'-acetyl KSM. Experimentally, KasF is unable to do so; both KasF and KasH are instead KSM-modifying enzymes, while the latter is more specific and reactive than the former in terms of the extent of resistance. The information gained here lays the foundation for mapping out the complete KSM biosynthetic pathway.

PubMed: 35203422
DOI: 10.3390/biomedicines10020212

Experimental method

X-RAY DIFFRACTION (2.58 Å)