Structure/Function Studies on a S-Adenosyl-l-methionine-dependent Uroporphyrinogen III C Methyltransferase (SUMT), a Key Regulatory Enzyme of Tetrapyrrole Biosynthesis

Vévodová, J.; Graham, Ross M.; Raux, Evelyne; Schubert, Heidi; Roper, David I.; Brindley, Amanda A.; Scott, A. Ian; Roessner, Charles A.; Stamford, N. Patrick J.; Stroupe, M. Elizabeth; Getzoff, Elizabeth D.; Warren, Martin J.; Wilson, K.S.

doi:10.1016/j.jmb.2004.09.020

Cited by 58 publications

(34 citation statements)

References 39 publications

(52 reference statements)

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“…In contrast, the biosyntheses of siroheme (163,164) and vitamin B 12 (165)(166)(167) involve the SAM-dependent methylation of the tetrapyrrole framework at positions C-2 and C-7. This is achieved by the action of an enzyme called S-adenosyl-L-methionine uroporphyrinogen III methyltransferase (SUMT), which specifically methylates uroporphyrinogen III at positions C-2 and C-7 in a SAM-dependent fashion to generate precorrin-2, or dihydrosirohydrochlorin (166,168) ( Fig. 10).…”

Section: Dailey Et Almentioning

confidence: 99%

Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product

Dailey

Gerdes³

et al. 2017

Microbiol Mol Biol Rev

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272

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SUMMARY The advent of heme during evolution allowed organisms possessing this compound to safely and efficiently carry out a variety of chemical reactions that otherwise were difficult or impossible. While it was long assumed that a single heme biosynthetic pathway existed in nature, over the past decade, it has become clear that there are three distinct pathways among prokaryotes, although all three pathways utilize a common initial core of three enzymes to produce the intermediate uroporphyrinogen III. The most ancient pathway and the only one found in the Archaea converts siroheme to protoheme via an oxygen-independent four-enzyme-step process. Bacteria utilize the initial core pathway but then add one additional common step to produce coproporphyrinogen III. Following this step, Gram-positive organisms oxidize coproporphyrinogen III to coproporphyrin III, insert iron to make coproheme, and finally decarboxylate coproheme to protoheme, whereas Gram-negative bacteria first decarboxylate coproporphyrinogen III to protoporphyrinogen IX and then oxidize this to protoporphyrin IX prior to metal insertion to make protoheme. In order to adapt to oxygen-deficient conditions, two steps in the bacterial pathways have multiple forms to accommodate oxidative reactions in an anaerobic environment. The regulation of these pathways reflects the diversity of bacterial metabolism. This diversity, along with the late recognition that three pathways exist, has significantly slowed advances in this field such that no single organism's heme synthesis pathway regulation is currently completely characterized.

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Section: Dailey Et Almentioning

confidence: 99%

Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product

Dailey

Gerdes³

et al. 2017

Microbiol Mol Biol Rev

Self Cite

272

335

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“…The synthesis of protoheme in D. vulgaris has been shown to involve precorrin-2 (dihydrosirohydrochlorin) as an intermediate (1, 10). Precorrin-2, which is a 2,7-dimethyl derivative of Uro III, is formed from Uro III in two consecutive methylation reactions with S-adenosyl-L-methionine as methyl donor (21) (Fig. 1).…”

mentioning

confidence: 99%

Heme Biosynthesis in Methanosarcina barkeri via a Pathway Involving Two Methylation Reactions

et al. 2006

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The methanogenic archaeon Methanosarcina barkeri synthesizes protoheme via precorrin-2, which is formed from uroporphyrinogen III in two consecutive methylation reactions utilizing S-adenosyl-L-methionine. The existence of this pathway, previously exclusively found in the sulfate-reducing ␦-proteobacterium Desulfovibrio vulgaris, was demonstrated for M. barkeri via the incorporation of two methyl groups from methionine into protoheme.

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“…For Pseudomonas denitrificans UPMT, some residues, including Asp47 and Leu49, are proposed to contribute to the binding of urogen III. The Asp47Asn and Leu49Ala mutants generate the first methylated intermediate, precorrin-1 (34). As the exact urogen III binding site in UPMT is not determined, we envisage that the possible roles of two amino acid residues in UPMT are similar to the roles of Asp78 and Met80 in UROD Bs .…”

Section: Discussionmentioning

confidence: 95%

“…At the same position on the side chains, decarboxylation is catalyzed by UROD. An aspartate in UPMT is proposed to interact with urogen III (33,34). For two branch-point enzymes sharing common initial substrates, the urogen III binding site is a big trough in UPMT and a deep cleft in UROD Bs , mainly due to the difference in the reactions catalyzed by the two respective enzymes.…”

Section: Discussionmentioning

confidence: 99%

Crystal Structure of Uroporphyrinogen Decarboxylase from Bacillus subtilis

et al. 2007

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Uroporphyrinogen decarboxylase (UROD) is a branch point enzyme in the biosynthesis of the tetrapyrroles. It catalyzes the decarboxylation of four acetate groups of uroporphyrinogen III to yield coproporphyrinogen III, leading to heme and chlorophyll biosynthesis. UROD is a special type of nonoxidative decarboxylase, since no cofactor is essential for catalysis. In this work, the first crystal structure of a bacterial UROD, Bacillus subtilis UROD (UROD Bs ), has been determined at a 2.3 Å resolution. The biological unit of UROD Bs was determined by dynamic light scattering measurements to be a homodimer in solution. There are four molecules in the crystallographic asymmetric unit, corresponding to two homodimers. Structural comparison of UROD Bs with eukaryotic URODs reveals a variation of two loops, which possibly affect the binding of substrates and release of products. Structural comparison with the human UROD-coproporphyrinogen III complex discloses a similar active cleft, with five invariant polar residues (Arg29, Arg33, Asp78, Tyr154, and His322) and three invariant hydrophobic residues (Ile79, Phe144, and Phe207), in UROD Bs . Among them, Asp78 may interact with the pyrrole NH groups of the substrate, and Arg29 is a candidate for positioning the acetate groups of the substrate. Both residues may also play catalytic roles.Tetrapyrroles, including heme, chlorophyll, siroheme, and vitamin B 12 , are a family of structurally related cofactors and prosthetic groups with different central metal ion insertions. The common pathways in tetrapyrrole biosynthesis start from the first precursor 5-aminolevulinate. Two molecules of this compound are condensed to generate porphobilinogen (PBG). Four molecules of PBG are further condensed by PBG deaminase (PBGD) to generate hydroxymethylbilane, which is subsequently cyclized to generate either uroporphyrinogen III (urogen III), by urogen III synthase with inversion of the D pyrrole ring, or isomer urogen I, by nonenzyme catalysis. urogen III is the last common precursor of all tetrapyrroles in living cells, at which major branching of the biosynthetic pathways happens. Bismethylation of urogen III by urogen methyltransferase (UPMT) generates procorrin-2, an intermediate in the biosynthesis of siroheme and vitamin B 12 .

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Structure/Function Studies on a S-Adenosyl-l-methionine-dependent Uroporphyrinogen III C Methyltransferase (SUMT), a Key Regulatory Enzyme of Tetrapyrrole Biosynthesis

Cited by 58 publications

References 39 publications

Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product

Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product

Heme Biosynthesis in Methanosarcina barkeri via a Pathway Involving Two Methylation Reactions

Crystal Structure of Uroporphyrinogen Decarboxylase from Bacillus subtilis

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