7CS0

Aminoglycoside 2'-N-acetyltransferase from Mycolicibacterium smegmatis-Complex with Coenzyme A and Paromomycin


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.183 
  • R-Value Observed: 0.186 

Starting Model: experimental
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Ligand Structure Quality Assessment 


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Literature

Structural and biochemical analyses of an aminoglycoside 2'-N-acetyltransferase from Mycolicibacterium smegmatis.

Jeong, C.S.Hwang, J.Do, H.Cha, S.S.Oh, T.J.Kim, H.J.Park, H.H.Lee, J.H.

(2020) Sci Rep 10: 21503-21503

  • DOI: https://doi.org/10.1038/s41598-020-78699-z
  • Primary Citation of Related Structures:  
    7CRM, 7CS0, 7CS1, 7CSI, 7CSJ

  • PubMed Abstract: 

    The expression of aminoglycoside-modifying enzymes represents a survival strategy of antibiotic-resistant bacteria. Aminoglycoside 2'-N-acetyltransferase [AAC(2')] neutralizes aminoglycoside drugs by acetylation of their 2' amino groups in an acetyl coenzyme A (CoA)-dependent manner. To understand the structural features and molecular mechanism underlying AAC(2') activity, we overexpressed, purified, and crystallized AAC(2') from Mycolicibacterium smegmatis [AAC(2')-Id] and determined the crystal structures of its apo-form and ternary complexes with CoA and four different aminoglycosides (gentamicin, sisomicin, neomycin, and paromomycin). These AAC(2')-Id structures unraveled the binding modes of different aminoglycosides, explaining the broad substrate specificity of the enzyme. Comparative structural analysis showed that the α4-helix and β8-β9 loop region undergo major conformational changes upon CoA and substrate binding. Additionally, structural comparison between the present paromomycin-bound AAC(2')-Id structure and the previously reported paromomycin-bound AAC(6')-Ib and 30S ribosome structures revealed the structural features of paromomycin that are responsible for its antibiotic activity and AAC binding. Taken together, these results provide useful information for designing AAC(2') inhibitors and for the chemical modification of aminoglycosides.


  • Organizational Affiliation

    Research Unit of Cryogenic Novel Material, Korea Polar Research Institute, Incheon, 21990, Republic of Korea.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Aminoglycoside 2'-N-acetyltransferase
A, B
210Mycolicibacterium smegmatis MC2 155Mutation(s): 0 
Gene Names: aacMSMEG_0434MSMEI_0423
EC: 2.3.1
UniProt
Find proteins for P94968 (Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155))
Explore P94968 
Go to UniProtKB:  P94968
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP94968
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
COA (Subject of Investigation/LOI)
Query on COA

Download Ideal Coordinates CCD File 
D [auth A],
K [auth B]
COENZYME A
C21 H36 N7 O16 P3 S
RGJOEKWQDUBAIZ-IBOSZNHHSA-N
PAR (Subject of Investigation/LOI)
Query on PAR

Download Ideal Coordinates CCD File 
C [auth A],
J [auth B]
PAROMOMYCIN
C23 H45 N5 O14
UOZODPSAJZTQNH-LSWIJEOBSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
E [auth A],
F [auth A],
L [auth B]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
ACT
Query on ACT

Download Ideal Coordinates CCD File 
G [auth A]ACETATE ION
C2 H3 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-M
CA
Query on CA

Download Ideal Coordinates CCD File 
H [auth A],
I [auth A],
M [auth B]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.183 
  • R-Value Observed: 0.186 
  • Space Group: P 32
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 56.374α = 90
b = 56.374β = 90
c = 122.866γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2021-06-23
    Type: Initial release
  • Version 1.1: 2023-11-29
    Changes: Data collection, Database references, Refinement description