6XUC

Structure of coproheme decarboxylase from Corynebacterium diphteriae in complex with coproheme


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.87 Å
  • R-Value Free: 0.223 
  • R-Value Work: 0.165 
  • R-Value Observed: 0.168 

Starting Model: experimental
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This is version 1.2 of the entry. See complete history


Literature

Actinobacterial Coproheme Decarboxylases Use Histidine as a Distal Base to Promote Compound I Formation.

Michlits, H.Lier, B.Pfanzagl, V.Djinovic-Carugo, K.Furtmuller, P.G.Oostenbrink, C.Obinger, C.Hofbauer, S.

(2020) ACS Catal 10: 5405-5418

  • DOI: https://doi.org/10.1021/acscatal.0c00411
  • Primary Citation of Related Structures:  
    6XUB, 6XUC

  • PubMed Abstract: 

    Coproheme decarboxylases (ChdCs) catalyze the final step in heme b biosynthesis of monoderm and some diderm bacteria. In this reaction, coproheme is converted to heme b via monovinyl monopropionate deuteroheme (MMD) in two consecutive decarboxylation steps. In Firmicutes decarboxylation of propionates 2 and 4 of coproheme depend on hydrogen peroxide and the presence of a catalytic tyrosine. Here we demonstrate that ChdCs from Actinobacteria are unique in using a histidine (H118 in ChdC from Corynebacterium diphtheriae , Cd ChdC) as a distal base in addition to the redox-active tyrosine (Y135). We present the X-ray crystal structures of coproheme- Cd ChdC and MMD- Cd ChdC, which clearly show (i) differences in the active site architecture between Firmicutes and Actinobacteria and (ii) rotation of the redox-active reaction intermediate (MMD) after formation of the vinyl group at position 2. Distal H118 is shown to catalyze the heterolytic cleavage of hydrogen peroxide ( k app = (4.90 ± 1.25) × 10 4 M -1 s -1 ). The resulting Compound I is rapidly converted to a catalytically active Compound I* (oxoiron(IV) Y135 ) that initiates the radical decarboxylation reactions. As a consequence of the more efficient Compound I formation, actinobacterial ChdCs exhibit a higher catalytic efficiency in comparison to representatives from Firmicutes. On the basis of the kinetic data of wild-type Cd ChdC and the variants H118A, Y135A, and H118A/Y135A together with high-resolution crystal structures and molecular dynamics simulations, we present a molecular mechanism for the hydrogen peroxide dependent conversion of coproheme via MMD to heme b and discuss differences between ChdCs from Actinobacteria and Firmicutes.


  • Organizational Affiliation

    Department of Chemistry, Institute of Biochemistry, BOKU-University of Natural Resources and Life Sciences, A-1190 Vienna, Austria.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Chlorite dismutase
A, B, C, D, E
237Corynebacterium diphtheriaeMutation(s): 0 
Gene Names: B11Q_01470BT093_04375
EC: 1.3.98.5
UniProt
Find proteins for Q6NGV6 (Corynebacterium diphtheriae (strain ATCC 700971 / NCTC 13129 / Biotype gravis))
Explore Q6NGV6 
Go to UniProtKB:  Q6NGV6
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6NGV6
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.87 Å
  • R-Value Free: 0.223 
  • R-Value Work: 0.165 
  • R-Value Observed: 0.168 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 61.021α = 90
b = 123.157β = 98.49
c = 77.893γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
PDB_EXTRACTdata extraction
EDNAdata reduction
EDNAdata scaling
PHENIXphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Austrian Science FundAustriaP29099

Revision History  (Full details and data files)

  • Version 1.0: 2020-04-22
    Type: Initial release
  • Version 1.1: 2020-06-10
    Changes: Database references
  • Version 1.2: 2024-01-24
    Changes: Data collection, Database references, Refinement description