2H2A

Crystal structure of Nicotinic acid mononucleotide adenylyltransferase from Staphylococcus aureus: product bound form 2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 

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This is version 1.3 of the entry. See complete history


Literature

Crystal Structure of Nicotinic Acid Mononucleotide Adenylyltransferase from Staphyloccocus aureus: Structural Basis for NaAD Interaction in Functional Dimer.

Han, S.Forman, M.D.Loulakis, P.Rosner, M.H.Xie, Z.Wang, H.Danley, D.E.Yuan, W.Schafer, J.Xu, Z.

(2006) J Mol Biol 360: 814-825

  • DOI: https://doi.org/10.1016/j.jmb.2006.05.055
  • Primary Citation of Related Structures:  
    2H29, 2H2A

  • PubMed Abstract: 

    Bacterial nicotinic acid mononucleotide adenylyltransferase (NaMNAT; EC 2.7.7.18) encoded by the nadD gene, is essential for cell survival and is thus an attractive target for developing new antibacterial agents. The NaMNAT catalyzes the transfer of an adenylyl group of ATP to nicotinic acid mononucleotide (NaMN) to form nicotinic acid dinucleotide (NaAD). Two independently derived, high-resolution structures of Staphylococcus aureus NaMNAT-NaAD complexes establish the conserved features of the core dinucleotide-binding fold with other adenylyltransferases from bacteria to human despite a limited sequence conservation. The crystal structures reveal that the nicotinate carboxylates of NaAD are recognized by interaction with the main-chain amides of Thr85 and Tyr117, a positive helix dipole and two bridged-water molecules. Unlike other bacterial adenylyltransferases, where a partially conserved histidine residue interacts with the nicotinate ring, the Leu44 side-chain interacts with the nicotinate ring by van der Waals contact. Importantly, the S. aureus NaMNAT represents a distinct adenylyltransferase subfamily identifiable in part by common features of dimerization and substrate recognition in the loop connecting beta5 to beta6 (residues 132-146) and the additional beta6 strand. The unique beta6 strand helps orient the residues in the loop connecting beta5 to beta6 for substrate/product recognition and allows the beta7 strand structural flexibility to make key dimer interface interactions. Taken together, these structural results provide a molecular basis for understanding the coupled activity and recognition specificity for S. aureus NaMNAT and for rational design of selective inhibitors.


  • Organizational Affiliation

    Pfizer Inc. Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. seungil.han@pfizer.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Probable nicotinate-nucleotide adenylyltransferase
A, B
189Staphylococcus aureusMutation(s): 1 
Gene Names: nadD
EC: 2.7.7.18
UniProt
Find proteins for Q5HFG7 (Staphylococcus aureus (strain COL))
Explore Q5HFG7 
Go to UniProtKB:  Q5HFG7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ5HFG7
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
CSX
Query on CSX
A, B
L-PEPTIDE LINKINGC3 H7 N O3 SCYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 62.303α = 90
b = 83.649β = 90
c = 99.113γ = 90
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

  • Released Date: 2006-08-08 
  • Deposition Author(s): Han, S.

Revision History  (Full details and data files)

  • Version 1.0: 2006-08-08
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description