4P53

ValA (2-epi-5-epi-valiolone synthase) from Streptomyces hygroscopicus subsp. jinggangensis 5008 with NAD+ and Zn2+ bound


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.262 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.183 

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This is version 1.4 of the entry. See complete history


Literature

Structure of a sedoheptulose 7-phosphate cyclase: ValA from Streptomyces hygroscopicus.

Kean, K.M.Codding, S.J.Asamizu, S.Mahmud, T.Karplus, P.A.

(2014) Biochemistry 53: 4250-4260

  • DOI: https://doi.org/10.1021/bi5003508
  • Primary Citation of Related Structures:  
    4P53

  • PubMed Abstract: 

    Sedoheptulose 7-phosphate cyclases (SH7PCs) encompass three enzymes involved in producing the core cyclitol structures of pseudoglycosides and similar bioactive natural products. One such enzyme is ValA from Streptomyces hygroscopicus subsp. jinggangensis 5008, which makes 2-epi-5-epi-valiolone as part of the biosynthesis of the agricultural antifungal agent validamycin A. We present, as the first SH7PC structure, the 2.1 Å resolution crystal structure of ValA in complex with NAD+ and Zn2+ cofactors. ValA has a fold and active site organization resembling those of the sugar phosphate cyclase dehydroquinate synthase (DHQS) and contains two notable, previously unrecognized interactions between NAD+ and Asp side chains conserved in all sugar phosphate cyclases that may influence catalysis. Because the domains of ValA adopt a nearly closed conformation even though no sugar substrate is present, comparisons with a ligand-bound DHQS provide a model for aspects of substrate binding. One striking active site difference is a loop that adopts a distinct conformation as a result of an Asp→Asn change with respect to DHQS and alters the identity and orientation of a key Arg residue. This and other active site differences in ValA are mostly localized to areas where the ValA substrate differs from that of DHQS. Sequence comparisons with a second SH7PC making a product with distinct stereochemistry lead us to postulate that the product stereochemistry of a given SH7PC is not the result of events taking place during catalysis but is accomplished by selective binding of either the α or β pyranose anomer of the substrate.


  • Organizational Affiliation

    Department of Biochemistry and Biophysics, Oregon State University , 2011 ALS Building, Corvallis, Oregon 97331-7305, United States.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cyclase420Streptomyces hygroscopicus subsp. jinggangensis 5008Mutation(s): 0 
Gene Names: SHJG_0276
UniProt
Find proteins for H2K887 (Streptomyces hygroscopicus subsp. jinggangensis (strain 5008))
Explore H2K887 
Go to UniProtKB:  H2K887
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupH2K887
Sequence Annotations
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  • Reference Sequence
Small Molecules
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.262 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.183 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 77.186α = 90
b = 77.186β = 90
c = 99.074γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
iMOSFLMdata reduction
SCALAdata scaling

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesR01AI061528

Revision History  (Full details and data files)

  • Version 1.0: 2014-07-30
    Type: Initial release
  • Version 1.1: 2014-10-01
    Changes: Database references
  • Version 1.2: 2017-09-20
    Changes: Advisory, Author supporting evidence, Database references, Derived calculations, Other, Refinement description, Source and taxonomy, Structure summary
  • Version 1.3: 2019-12-11
    Changes: Advisory, Author supporting evidence, Derived calculations
  • Version 1.4: 2023-09-27
    Changes: Data collection, Database references, Refinement description