7BVF

Cryo-EM structure of Mycobacterium tuberculosis arabinosyltransferase EmbA-EmbB-AcpM2 in complex with ethambutol


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 2.97 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol.

Zhang, L.Zhao, Y.Gao, Y.Wu, L.Gao, R.Zhang, Q.Wang, Y.Wu, C.Wu, F.Gurcha, S.S.Veerapen, N.Batt, S.M.Zhao, W.Qin, L.Yang, X.Wang, M.Zhu, Y.Zhang, B.Bi, L.Zhang, X.Yang, H.Guddat, L.W.Xu, W.Wang, Q.Li, J.Besra, G.S.Rao, Z.

(2020) Science 368: 1211-1219

  • DOI: https://doi.org/10.1126/science.aba9102
  • Primary Citation of Related Structures:  
    7BVC, 7BVE, 7BVF, 7BVG, 7BVH

  • PubMed Abstract: 

    The arabinosyltransferases EmbA, EmbB, and EmbC are involved in Mycobacterium tuberculosis cell wall synthesis and are recognized as targets for the anti-tuberculosis drug ethambutol. In this study, we determined cryo-electron microscopy and x-ray crystal structures of mycobacterial EmbA-EmbB and EmbC-EmbC complexes in the presence of their glycosyl donor and acceptor substrates and with ethambutol. These structures show how the donor and acceptor substrates bind in the active site and how ethambutol inhibits arabinosyltransferases by binding to the same site as both substrates in EmbB and EmbC. Most drug-resistant mutations are located near the ethambutol binding site. Collectively, our work provides a structural basis for understanding the biochemical function and inhibition of arabinosyltransferases and the development of new anti-tuberculosis agents.


  • Organizational Affiliation

    Shanghai Institute for Advanced Immunochemical Studies, iHuman Institute, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Probable arabinosyltransferase BA [auth B]1,116Mycobacterium tuberculosis H37RvMutation(s): 0 
Gene Names: embBRv3795MTCY13D12.29
EC: 2.4.2
Membrane Entity: Yes 
UniProt
Find proteins for P9WNL7 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WNL7 
Go to UniProtKB:  P9WNL7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WNL7
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Probable arabinosyltransferase AB [auth A]1,102Mycobacterium tuberculosis H37RvMutation(s): 0 
Gene Names: embARv3794MTCY13D12.28
EC: 2.4.2
Membrane Entity: Yes 
UniProt
Find proteins for P9WNL9 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WNL9 
Go to UniProtKB:  P9WNL9
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WNL9
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Meromycolate extension acyl carrier proteinC [auth P]99Mycolicibacterium smegmatis MC2 155Mutation(s): 0 
UniProt
Find proteins for A0R0B3 (Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155))
Explore A0R0B3 
Go to UniProtKB:  A0R0B3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0R0B3
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 2.97 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
MODEL REFINEMENTPHENIX1.16

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Chinese Academy of SciencesChinaXDB29020000
National Natural Science Foundation of China (NSFC)China81520108019
Ministry of Science and Technology (MoST, China)China2017YFC0840300
Medical Research Council (MRC, United Kingdom)United KingdomMR/S000542/1

Revision History  (Full details and data files)

  • Version 1.0: 2020-04-29
    Type: Initial release
  • Version 1.1: 2020-05-13
    Changes: Database references
  • Version 1.2: 2020-07-01
    Changes: Database references
  • Version 1.3: 2024-03-27
    Changes: Data collection, Database references