8JAB

Crystal structure of Mycobacterium tuberculosis LpqY in complex with trehalose analogue YB-06

Summary for 8JAB

• Entry DOI: 10.2210/pdb8jab/pdb
• Descriptor: Trehalose-binding lipoprotein LpqY, (2~{S},3~{S},4~{R},5~{S},6~{R})-2-(fluoranylmethyl)-6-[(2~{R},3~{R},4~{S},5~{S},6~{S})-6-(fluoranylmethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-oxane-3,4,5-triol, SULFATE ION, ... (4 entities in total)
• Functional Keywords: sugar binding protein
• Biological source: Mycobacterium tuberculosis H37Rv
• Total number of polymer chains: 1
• Total formula weight: 50629.67

Authors

Zhang, B.,Liang, J.,Rao, Z. (deposition date: 2023-05-05, release date: 2023-09-27, Last modification date: 2024-10-16)

Primary citation

Liang, J.,Liu, F.,Xu, P.,Shangguan, W.,Hu, T.,Wang, S.,Yang, X.,Xiong, Z.,Yang, X.,Guddat, L.W.,Yu, B.,Rao, Z.,Zhang, B.
Molecular recognition of trehalose and trehalose analogues by Mycobacterium tuberculosis LpqY-SugABC.
Proc.Natl.Acad.Sci.USA, 120:e2307625120-e2307625120, 2023

PubMed Abstract: Trehalose plays a crucial role in the survival and virulence of the deadly human pathogen (). The type I ATP-binding cassette (ABC) transporter LpqY-SugABC is the sole pathway for trehalose to enter . The substrate-binding protein, LpqY, which forms a stable complex with the translocator SugABC, recognizes and captures trehalose and its analogues in the periplasmic space, but the precise molecular mechanism for this process is still not well understood. This study reports a 3.02-Å cryoelectron microscopy structure of trehalose-bound LpqY-SugABC in the pretranslocation state, a crystal structure of LpqY in a closed form with trehalose bound and five crystal structures of LpqY in complex with different trehalose analogues. These structures, accompanied by substrate-stimulated ATPase activity data, reveal how LpqY recognizes and binds trehalose and its analogues, and highlight the flexibility in the substrate binding pocket of LpqY. These data provide critical insights into the design of trehalose analogues that could serve as potential molecular probe tools or as anti-TB drugs.

PubMed: 37603751
DOI: 10.1073/pnas.2307625120

Experimental method

X-RAY DIFFRACTION (1.7 Å)