PDBsum entry 1mvn

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Lyase PDB id
Protein chain
182 a.a. *
Waters ×42
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Ppc decarboxylase mutant c175s complexed with pantothenoylaminoethenethiol
Structure: Ppc decarboxylase athal3a. Chain: a. Synonym: halotolerance protein hal3a. Engineered: yes. Mutation: yes
Source: Arabidopsis thaliana. Thale cress. Organism_taxid: 3702. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Trimer (from PDB file)
2.21Å     R-factor:   0.210     R-free:   0.264
Authors: S.Steinbacher,P.Hernandez-Acosta,B.Bieseler,M.Blaesse,R.Hube F.A.Culianez-Macia,T.Kupke
Key ref:
S.Steinbacher et al. (2003). Crystal structure of the plant PPC decarboxylase AtHAL3a complexed with an ene-thiol reaction intermediate. J Mol Biol, 327, 193-202. PubMed id: 12614618 DOI: 10.1016/S0022-2836(03)00092-5
26-Sep-02     Release date:   04-Mar-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q9SWE5  (HAL3A_ARATH) -  Phosphopantothenoylcysteine decarboxylase
209 a.a.
182 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Phosphopantothenoylcysteine decarboxylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Coenzyme A Biosynthesis (late stages)
      Reaction: N-((R)-4'-phosphopantothenoyl)-L-cysteine = pantotheine 4'-phosphate + CO2
= pantotheine 4'-phosphate
+ CO(2)
      Cofactor: FMN
Bound ligand (Het Group name = FMN) corresponds exactly
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytosol   1 term 
  Biological process     regulation of growth   3 terms 
  Biochemical function     catalytic activity     4 terms  


    Added reference    
DOI no: 10.1016/S0022-2836(03)00092-5 J Mol Biol 327:193-202 (2003)
PubMed id: 12614618  
Crystal structure of the plant PPC decarboxylase AtHAL3a complexed with an ene-thiol reaction intermediate.
S.Steinbacher, P.Hernández-Acosta, B.Bieseler, M.Blaesse, R.Huber, F.A.Culiáñez-Macià, T.Kupke.
The Arabidopsis thaliana protein AtHAL3a decarboxylates 4'-phosphopantothenoylcysteine to 4'-phosphopantetheine, a step in coenzyme A biosynthesis. Surprisingly, this decarboxylation reaction is carried out as an FMN-dependent redox reaction. In the first half-reaction, the side-chain of the cysteine residue of 4'-phosphopantothenoylcysteine is oxidised and the thioaldehyde intermediate decarboxylates spontaneously to the 4'-phosphopantothenoyl-aminoethenethiol intermediate. In the second half-reaction this compound is reduced to 4'-phosphopantetheine and the FMNH(2) cofactor is re-oxidised. The active site mutant C175S is unable to perform this reductive half-reaction. Here, we present the crystal structure of the AtHAL3a mutant C175S in complex with the reaction intermediate pantothenoyl-aminoethenethiol and FMNH(2). The geometry of binding suggests that reduction of the C(alpha)=C(beta) double bond of the intermediate can be performed by direct hydride-transfer from N5 of FMNH(2) to C(beta) of the aminoethenethiol-moiety supported by a protonation of C(alpha) by Cys175. The binding mode of the substrate is very similar to that previously observed for a pentapeptide to the homologous enzyme EpiD that introduces the aminoethenethiol-moiety as final reaction product at the C terminus of peptidyl-cysteine residues. This finding further supports our view that these homologous enzymes form a protein family of homo-oligomeric flavin-containing cysteine decarboxylases, which we have termed HFCD family.
  Selected figure(s)  
Figure 1.
Figure 1. Reaction catalysed by AtHAL3a. The enzyme converts both PC (used in this study) and its 4'-phosphorylated derivative PPC, the native substrate. PC is oxidised to a thio-aldehyde intermediate that undergoes spontaneous decarboxylation to form OxPC. In the wild-type enzyme this intermediate is reduced to pantetheine.
Figure 6.
Figure 6. Proposed reaction mechanism. In the oxidative half-reaction a thiolate ion is stabilised by His90 and bound near the dimethylbenzene ring of FMN. Electrons are transferred by an SET mechanism from the thiolate to FMN and C^b is deprotonated. The resulting thioaldehyde intermediate decarboxylates spontaneously and tautomerisation leads to the formation of a cis ene-thiolate that binds to a cavity above the pyrimidine moiety of FMN. In that geometry OxPC can be reduced by direct hydride transfer from FMNH[2] to the C^b atom and the concomitant protonation of the C^a atom by Cys175.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 327, 193-202) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20821290 D.Chao, and H.Lin (2010).
The tricks plants use to reach appropriate light.
  Sci China Life Sci, 53, 916-926.  
19543273 S.Y.Sun, D.Y.Chao, X.M.Li, M.Shi, J.P.Gao, M.Z.Zhu, H.Q.Yang, S.Luan, and H.X.Lin (2009).
OsHAL3 mediates a new pathway in the light-regulated growth of rice.
  Nat Cell Biol, 11, 845-851.  
16963440 M.Goto, H.Hayashi, I.Miyahara, K.Hirotsu, M.Yoshida, and T.Oikawa (2006).
Crystal structures of nonoxidative zinc-dependent 2,6-dihydroxybenzoate (gamma-resorcylate) decarboxylase from Rhizobium sp. strain MTP-10005.
  J Biol Chem, 281, 34365-34373.
PDB codes: 2dvt 2dvu 2dvx
16371361 T.Kupke, and W.Schwarz (2006).
4'-phosphopantetheine biosynthesis in Archaea.
  J Biol Chem, 281, 5435-5444.  
16453030 T.P.Begley (2006).
Cofactor biosynthesis: an organic chemist's treasure trove.
  Nat Prod Rep, 23, 15-25.  
15593134 E.Strauss, and T.P.Begley (2005).
The selectivity for cysteine over serine in coenzyme A biosynthesis.
  Chembiochem, 6, 284-286.  
15192104 A.Ruiz, I.Muñoz, R.Serrano, A.González, E.Simón, and J.Ariño (2004).
Functional characterization of the Saccharomyces cerevisiae VHS3 gene: a regulatory subunit of the Ppz1 protein phosphatase with novel, phosphatase-unrelated functions.
  J Biol Chem, 279, 34421-34430.  
15459342 E.S.Rangarajan, Y.Li, P.Iannuzzi, A.Tocilj, L.W.Hung, A.Matte, and M.Cygler (2004).
Crystal structure of a dodecameric FMN-dependent UbiX-like decarboxylase (Pad1) from Escherichia coli O157: H7.
  Protein Sci, 13, 3006-3016.
PDB code: 1sbz
15292171 I.Muñoz, A.Ruiz, M.Marquina, A.Barceló, A.Albert, and J.Ariño (2004).
Functional characterization of the yeast Ppz1 phosphatase inhibitory subunit Hal3: a mutagenesis study.
  J Biol Chem, 279, 42619-42627.  
14686929 T.Kupke (2004).
Active-site residues and amino acid specificity of the bacterial 4'-phosphopantothenoylcysteine synthetase CoaB.
  Eur J Biochem, 271, 163-172.  
12876343 M.Blaesse, T.Kupke, R.Huber, and S.Steinbacher (2003).
Structure of MrsD, an FAD-binding protein of the HFCD family.
  Acta Crystallogr D Biol Crystallogr, 59, 1414-1421.
PDB code: 1p3y
14501115 N.Manoj, and S.E.Ealick (2003).
Unusual space-group pseudosymmetry in crystals of human phosphopantothenoylcysteine decarboxylase.
  Acta Crystallogr D Biol Crystallogr, 59, 1762-1766.
PDB code: 1qzu
12860978 T.Kupke, P.Hernández-Acosta, and F.A.Culiáñez-Macià (2003).
4'-phosphopantetheine and coenzyme A biosynthesis in plants.
  J Biol Chem, 278, 38229-38237.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.