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Overview for MACiE Entry M0201

Version history

General Information

EC Number: 6.4.1.3 (A member of the Ligases, Forming carbon-carbon bonds, Ligases that form carbon-carbon bonds (only sub-subclass identified to date))

Enzyme Name: propionyl-CoA carboxylase

Biological Species: Streptomyces coelicolor (Bacteria)

Catalytic Chain UniprotKB Accession Codes:

Representative PDB Code: 1xny - BIOTIN AND PROPIONYL-COA BOUND TO ACYL-COA CARBOXYLASE BETA SUBUNITFROM S. COELICOLOR (PCCB) (Resolution = 2.20 Å).

Catalytic CATH Codes:

Display structure information

Overall Reaction:

Image of ATP

Image of bicarbonate

Image of propanoyl-CoA

right arrow

Image of proton

Image of (S)-2-methyl-3-oxopropanoyl-CoA

Image of phosphate

Image of ADP

ATP
C00002
CHEBI:30616
bicarbonate
C00288
CHEBI:17544
propanoyl-CoA
C00100
CHEBI:57392
proton
C00080
CHEBI:24636
(S)-2-methyl-3-oxopropanoyl-CoA
C00683
CHEBI:57326
phosphate
C00009
CHEBI:18367
ADP
C00008
CHEBI:456216

Overall Comment: The enzyme consists of two polypeptides: an alpha-subunit containing the BC and BCCP domains and a beta-subunit corresponding to the CT domain [2]. BC catalyses carboxylation of the biotin attached to the biotin carboxyl carrier protein (BCCP) in a reaction that requires ATP Mg(II) and bicarbonate (steps 1 to 4)[1]. However no structural data is reported for this subunit thus the function of the magnesium ion and the identity of the catalytic base are unknown. CT catalyses the carboxyl transfer from biotin to propanoyl-CoA (steps 5 to 7)[1 2]. This subunit corresponds to PDB code 1xny. BTN5600 is the biotin cofactor which in the physiological enzyme is attached to a Lysine residue in the BCCP domain. An alternative acid catalysed mechanism for steps 5 to 7 should be chemically feasible and has previously been observed for Carboxybiotin Carboxyimidazolidone and Carbamates. However the required acid and base could not be identified in the active site.

The enzyme does not return to a state in which it can catalyse another reaction


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Stepwise Description of the Reaction

Step 1Reaction occurs in the alpha-subunit. The bicarbonate is deprotonated by an unidentified base. The activate bicarbonate then acts as a nucleophile and attacks the gamma-phosphate in a substitution reaction, liberating ADP. Mg(II) stabilises/activates the ATP
Step 2Reaction occurs in the alpha-subunit. The phosphorylated bicarbonate undergoes a decarboxylation reaction (E1cb) to liberate carbon dioxide and phosphate.
Step 3Reaction occurs in the alpha-subunit. The phosphate deprotonates one of the N-H groups of biotin with concomitant tautomerisation to produce an oxyanion.
Step 4Reaction occurs in the alpha-subunit. The oxyanion re-forms the carbonyl group, causing the C=N bond of the activated biotin to add to the carbon dioxide in a nucleophilic manner.
Step 5Reaction occurs in the beta-subunit. Once the carboxylated biotin has relocated to the beta-subunit, the biotin undergoes a decarboxylation reaction (E1cb) to liberate carbon dioxide and the activated biotin molecule. the main chain amides of Gly419B and Ala420B stabilise the oxyanion of the activated biotin.
Step 6Reaction occurs in the beta-subunit. The oxyanion re-forms the carbonyl group, causing the C=N bond of the activated biotin to deprotonate the propanoyl-CoA with concomitant tautomerisation. The main chain amides of Gly182 and Gly183 stabilise the activated propanoyl-CoA, the main chain amides of Gly419B and Ala420B stabilise the oxyanion of the activated biotin.
Step 7Reaction occurs in the beta-subunit. The oxyanion re-forms the carbonyl group causing the C=C bond of the activated propanoyl-CoA to add to the carbon dioxide molecule in an electrophilic manner.

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Catalytic Residues Involved

Type Number Chain Location of Function
Gly 182 A Main Chain Amide
Gly 183 A Main Chain Amide
Gly 419 B Main Chain Amide
Ala 420 B Main Chain Amide

Organic Cofactors for M0201

Type Identity Chain
Biotin BTN 5600 Overview

Metal Cofactors for M0201

Type Het group Number Chain
magnesium MG(not in PDB) 1 x Overview

References

  1. J. R. Knowles (1989), Annu. Rev. Biochem., 58, 195-221. The mechanism of biotin-dependent enzymes.
    Medline: 2673009
  2. L. Diacovich et al. (2004), Biochemistry, 43, 14027-14036. Crystal structure of the beta-subunit of acyl-CoA carboxylase: structure-based engineering of substrate specificity.
    Medline: 15518551

Homologue information for M0201 (1xny)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)



Entries with at least one Catalytic CATH code in common (different mechanisms):

MACiE Entry Enzyme Name
EC Number
PDB code CATH code Composite
Reaction Similarity
Catalytic Machinery
Similarity
M0024 4-chlorobenzoyl-CoA dehalogenase
3.8.1.7
1nzy 3.90.226.10
0.29670.2999Compare
M0070 methylmalonyl-CoA decarboxylase
4.1.1.41
1ef8 3.90.226.10
0.12320.27Compare
M0346 1,4-dihydroxy-2-naphthoyl-CoA synthase
4.1.3.36
1q51 3.90.226.10
0.32780.4796Compare
M0315 enoyl-CoA hydratase
4.2.1.17
1ey3 3.90.226.10
0.10250.3249Compare
M0343 methylglutaconyl-CoA hydratase
4.2.1.18
1hzd 3.90.226.10
0.10250.3211Compare
M0342 delta(3,5)-delta(2,4)-dienoyl-CoA isomerase
5.3.3.-
1dci 3.90.226.10
0.0120.0226Compare
M0341 dodecenoyl-CoA isomerase
5.3.3.8
1sg4 3.90.226.10
0.12820.27Compare

View a comparison of the other reactions in MACiE with the CATH domain 3.90.226.10


Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
Link to MetaCyc Link to KEGG Link to BRENDA Link to ExplorENZ

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acetyl-CoA carboxylase activity (molecular function)
fatty acid biosynthetic process (biological process)
acetyl-CoA carboxylase complex (cellular component)
ligase activity (molecular function)
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