RCSB PDB - 8VZA: Crystal Structure of 2-Hydroxacyl-CoA Lyase/Synthase ApbHACS from Alphaproteobacteria bacterium in the Complex with THDP, L-Lactyl-CoA, and ADP

 8VZA

Crystal Structure of 2-Hydroxacyl-CoA Lyase/Synthase ApbHACS from Alphaproteobacteria bacterium in the Complex with THDP, L-Lactyl-CoA, and ADP


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.208 

Starting Model: in silico
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wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted UQ3Click on this verticalbar to view detailsBest fitted 8FLClick on this verticalbar to view detailsBest fitted ADPClick on this verticalbar to view details

This is version 1.0 of the entry. See complete history


Literature

Revealing reaction intermediates in one-carbon elongation by thiamine diphosphate/CoA-dependent enzyme family.

Kim, Y.Lee, S.H.Gade, P.Nattermann, M.Maltseva, N.Endres, M.Chen, J.Wichmann, P.Hu, Y.Marchal, D.G.Yoshikuni, Y.Erb, T.J.Gonzalez, R.Michalska, K.Joachimiak, A.

(2024) Commun Chem 7: 160-160

  • DOI: https://doi.org/10.1038/s42004-024-01242-y
  • Primary Citation of Related Structures:  
    8VZA, 8VZB, 8VZC, 8VZD, 8VZE, 8VZF, 8VZH, 8VZI, 8VZJ, 8VZK

  • PubMed Abstract: 

    2-Hydroxyacyl-CoA lyase/synthase (HACL/S) is a thiamine diphosphate (ThDP)-dependent versatile enzyme originally discovered in the mammalian α-oxidation pathway. HACL/S natively cleaves 2-hydroxyacyl-CoAs and, in its reverse direction, condenses formyl-CoA with aldehydes or ketones. The one-carbon elongation biochemistry based on HACL/S has enabled the use of molecules derived from greenhouse gases as biomanufacturing feedstocks. We investigated several HACL/S family members with high activity in the condensation of formyl-CoA and aldehydes, and distinct chain-length specificities and kinetic parameters. Our analysis revealed the structures of enzymes in complex with acyl-CoA substrates and products, several covalent intermediates, bound ThDP and ADP, as well as the C-terminal active site region. One of these observed states corresponds to the intermediary α-carbanion with hydroxymethyl-CoA covalently attached to ThDP. This research distinguishes HACL/S from related sub-families and identifies key residues involved in substrate binding and catalysis. These findings expand our knowledge of acyloin-condensation biochemistry and offer attractive prospects for biocatalysis using carbon elongation.


  • Organizational Affiliation

    eBERlight and Structural Biology Center, X-ray Science Division, Argonne National Laboratory, Lemont, IL, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
2-Hydroxyacyl-CoA lyase/Synthase
A, B, C, D
560Alphaproteobacteria bacteriumMutation(s): 0 
Gene Names: DCO82_10540
EC: 4.1.1.8
UniProt
Find proteins for A0A3C0TX30 (Alphaproteobacteria bacterium)
Explore A0A3C0TX30 
Go to UniProtKB:  A0A3C0TX30
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A3C0TX30
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 6 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
UQ3 (Subject of Investigation/LOI)
Query on UQ3

Download Ideal Coordinates CCD File 
F [auth A],
L [auth B],
Q [auth C],
W [auth D]
S-{(3S,5R,9R)-1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)oxolan-2-yl]-3,5,9-trihydroxy-8,8-dimethyl-3,5,10,14-tetraoxo-2,4,6-trioxa-11,15-diaza-3lambda~5~,5lambda~5~-diphosphaheptadecan-17-yl} (2R)-2-hydroxypropanethioate
C24 H40 N7 O18 P3 S
VIWKEBOLLIEAIL-AGCMQPJKSA-N
8FL (Subject of Investigation/LOI)
Query on 8FL

Download Ideal Coordinates CCD File 
E [auth A],
K [auth B],
P [auth C],
V [auth D]
2-[(2R)-3-[(4-azanyl-2-methyl-pyrimidin-5-yl)methyl]-4-methyl-2-oxidanyl-2H-1,3-thiazol-5-yl]ethyl phosphono hydrogen phosphate
C12 H20 N4 O8 P2 S
GFCMTWPFATXWRY-GFCCVEGCSA-N
ADP (Subject of Investigation/LOI)
Query on ADP

Download Ideal Coordinates CCD File 
G [auth A],
M [auth B],
S [auth C],
X [auth D]
ADENOSINE-5'-DIPHOSPHATE
C10 H15 N5 O10 P2
XTWYTFMLZFPYCI-KQYNXXCUSA-N
GOL
Query on GOL

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N [auth B]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
ACE
Query on ACE

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H [auth A],
J [auth B],
R [auth C],
T [auth C]
ACETYL GROUP
C2 H4 O
IKHGUXGNUITLKF-UHFFFAOYSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
I [auth A],
O [auth B],
U [auth C],
Y [auth D]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.208 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 69.409α = 114.1
b = 102.679β = 96.74
c = 104.344γ = 105.23
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-3000data reduction
HKL-3000data scaling
HKL-3000phasing
MOLREPphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted UQ3Click on this verticalbar to view detailsBest fitted 8FLClick on this verticalbar to view detailsBest fitted ADPClick on this verticalbar to view details

Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Department of Energy (DOE, United States)United States--

Revision History  (Full details and data files)

  • Version 1.0: 2024-10-02
    Type: Initial release