Enzyme - Uroporphyrinogen-III C-methyltransferase

Alternative Name(s)
  • S-adenosyl-L-methionine-dependent uroporphyrinogen III methylase.
  • Uroporphyrin-III C-methyltransferase.
  • Urogen III methylase.
  • Adenosylmethionine-uroporphyrinogen III methyltransferase.
  • SUMT.
  • Uroporphyrinogen-III methyltransferase.
  • Uroporphyrinogen-III methylase.
  • Uroporphyrinogen III methylase.
  • Uroporphyrinogen methyltransferase.

Catalytic Activity

2 S-adenosyl-L-methionine + uroporphyrinogen III = H(+) + precorrin-2 + 2 S-adenosyl-L-homocysteine


There are no Cofactors for this Enzyme

Reaction Mechanism

    The reference protein (CysG) covers three different domains/functions each component of which can be found as independent proteins in other organisms. This entry relates to the uroporphyrinogen-III C-methyltransferase function (residues 216-448 in the reference protein). This catalytic site catalyses two sequential methylation reactions using S-andenosyl-L-methionine (SAM), the first forming precorrin-1 and the second leading to the formation of precorrin-2. It is the first of three steps leading to the formation of siroheme from uroporphyrinogen III.

    The methyl transfers occur through SN2 type reactions in which the incoming methyl group undergoes stereochemical inversion. The nitrogen lone pair of ring A activates carbon C2 which subsequently performs nucleophilic attack on the methyl group bound to the sulfur of SAM. Asp248 carboxylate group abstracts a proton from the tetrapyrrole ring. Lys270 could serve as a general acid to promote tautomerization of the tetrapyrrole, facilitating proton abstraction by Asp248. The resultant rearrangement of double bonds (C1-NH+ and C3-C4 to C20-C1 and C4-C5 respectively) forms precorrin-1. The resultant S-adenosyl-L-homocystine (SAH) and precorrin-1 are lost from the active site followed by binding of new SAM and precorrin-1 in a new orientation placing C7 in the correct position for methylation. The above process is repeated at C7, forming a second SAH and precorrin-2.
    Catalytic Residues
    AA Uniprot Uniprot Resid PDB PDB Resid
    Asp P25924 248 1pjq 248
    Lys P25924 270 1pjq 270
    Met P25924 382 1pjq 382
    Step Components

    intermediate formation, native state of enzyme regenerated, overall reactant used, bimolecular nucleophilic substitution, tautomerisation (not keto-enol), proton transfer, overall product formed

    Step 1.

    A methyl group from SAM is added to C2 of the pyrrole ring in a biomolecular nucleophilic substitution reaction.

    Step 2.

    Asp 248 accepts a proton from the intermediate, causing tautomerization of the tetrapyrrole.

    Step 3.

    Further tautomerization of the enamine occurs and precorrin 1 is formed.

    Step 4.

    A methyl group is added to precorrin-1 by SAM in a bimolecular nucleophilic substitution reaction.

    Step 5.

    Asp248 deprotonates the intermediate. Subsequent rearrangement of the resulting enamine double bond forms precorrin 2.

    Step 6.

    In an inferred step Asp248 is deprotonated to regenerate the native state of the enzyme.


    The products of the reaction.

Reaction Parameters

  • Kinetic Parameters
    Organism KM Value [mM] Substrate Comment
    Pseudomonas denitrificans (nom. rej.) 0.0063 S-adenosyl-L-methionine
    Desulfovibrio vulgaris 0.0004 uroporphyrinogen III pH 8.0, 22°C, CobA/HemD
    Staphylococcus aureus 0.00124 uroporphyrinogen III pH 8.0, temperature not specified in the publication
    Methanobacterium ivanovii 0.052 uroporphyrinogen III pH 7.7, 30°C
  • Temperature

    There are no reaction parameters information for this Enzyme.

  • pH

    There are no reaction parameters information for this Enzyme.

Associated Proteins

Protein name Organism
Probable uroporphyrinogen-III C-methyltransferase Fission yeast
S-adenosyl-L-methionine-dependent uroporphyrinogen III methyltransferase Methanosarcina barkeri (strain Fusaro / DSM 804)
Uroporphyrinogen-III C-methyltransferase Baker's yeast
Porphyrin biosynthesis protein HemD Ruminiclostridium josui
Siroheme synthase 1 Aeromonas hydrophila subsp. hydrophila (strain ATCC 7966 / DSM 30187 / JCM 1027 / KCTC 2358 / NCIMB 9240)