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Evolutionary relationships between heme-binding ferredoxin α + β barrels.

Acharya G, Kaur G, Subramanian S - BMC Bioinformatics (2016)

Bottom Line: We analyze the heme-binding sites in these proteins as well as their barrel topologies.We examine the heme-binding pockets and explore the versatility of the α + β barrels ability to accommodate heme or heme-related moieties, such as siroheme, in at least three different sites, namely, the mode seen in IsdG/OxdA, Cld/DyP/EfeB/HemQ and siroheme decarboxylase barrels.Our study offers insights into the plausible evolutionary relationships between the two distinct barrel packing topologies and relate the observed heme-binding sites to these topologies.

View Article: PubMed Central - PubMed

Affiliation: CSIR-Institute of Microbial Technology (IMTECH), Sector 39-A, Chandigarh, India.

ABSTRACT

Background: The α + β barrel superfamily of the ferredoxin-like fold consists of a functionally diverse group of evolutionarily related proteins. The barrel architecture of these proteins is formed by either homo-/hetero-dimerization or duplication and fusion of ferredoxin-like domains. Several members of this superfamily bind heme in order to carry out their functions.

Results: We analyze the heme-binding sites in these proteins as well as their barrel topologies. Our comparative structural analysis of these heme-binding barrels reveals two distinct modes of packing of the ferredoxin-like domains to constitute the α + β barrel, which is typified by the Type-1/IsdG-like and Type-2/OxdA-like proteins, respectively. We examine the heme-binding pockets and explore the versatility of the α + β barrels ability to accommodate heme or heme-related moieties, such as siroheme, in at least three different sites, namely, the mode seen in IsdG/OxdA, Cld/DyP/EfeB/HemQ and siroheme decarboxylase barrels.

Conclusions: Our study offers insights into the plausible evolutionary relationships between the two distinct barrel packing topologies and relate the observed heme-binding sites to these topologies.

No MeSH data available.


Representative structures of the heme-binding ferredoxin α + β barrel superfamily. (a) Ribbon diagram of the structures of OxdA (PDB identifier 3A16), Cld (PDB identifier 3NN1), MhuD (PDB identifier 3HX9), IsdG (PDB identifier 2ZDP), DyP (PDB identifier 3VXJ) and Siroheme decarboxylase (PDB identifier 4UN1). The individual ferredoxin-like folds in all structures have been colored from their N- to C-termini in chainbow coloring scheme of PyMOL and are faded to highlight the position of heme (magenta). Elements that do not constitute a part of the core of the ferredoxin-like fold are colored white. (b) A comparison of heme binding sites using topology diagrams. (c) Orientation of heme-moieties in different proteins of the ferredoxin α + β barrel superfamily. Here, the porphyrin ring of heme and siroheme substituents is shown as a rectangle and the extensions from the rectangle denote the propionate side chains
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Fig1: Representative structures of the heme-binding ferredoxin α + β barrel superfamily. (a) Ribbon diagram of the structures of OxdA (PDB identifier 3A16), Cld (PDB identifier 3NN1), MhuD (PDB identifier 3HX9), IsdG (PDB identifier 2ZDP), DyP (PDB identifier 3VXJ) and Siroheme decarboxylase (PDB identifier 4UN1). The individual ferredoxin-like folds in all structures have been colored from their N- to C-termini in chainbow coloring scheme of PyMOL and are faded to highlight the position of heme (magenta). Elements that do not constitute a part of the core of the ferredoxin-like fold are colored white. (b) A comparison of heme binding sites using topology diagrams. (c) Orientation of heme-moieties in different proteins of the ferredoxin α + β barrel superfamily. Here, the porphyrin ring of heme and siroheme substituents is shown as a rectangle and the extensions from the rectangle denote the propionate side chains

Mentions: Heme, a metal-porphyrin compound, is associated with at least six different families of this superfamily [2, 10, 12, 13]. Of these, three families, namely, Cld, DyP and aldoxime dehydratase (OxdA, PF13816) have been identified to bind heme as a cofactor [12–14], while IsdG and HemQ bind heme as a substrate and product, respectively [9, 10] (Fig. 1a). For members of the EfeB family, heme has been proposed to play a role in the assimilation of iron [15] and in the extra-cytoplasmic transport of the protein [16]. Heme is seen to bind at two spatially distinct regions in the barrel [2]. IsdG [17], HmoB [18], MhuD [19] and OxdA [14] share similar spatial location of the heme-binding site [2], while Cld [20], DyP [21] and EfeB [22] bind heme at a different location [2]. The exact location of the heme-binding histidine and orientation of the heme moiety vary even among proteins with the similar spatial location of heme [2] (Fig. 1b, c). In addition to these heme-binding families, a recently structurally characterized protein, siroheme decarboxylase, which is a member of the AsnC transcription regulator family, is known to function in the alternative heme biosynthesis pathway in some bacteria and archaea [23, 24]. Siroheme decarboxylase has been shown to bind siroheme, a metabolic intermediate in the alternative heme synthesis pathway, and convert it to didecarboxysiroheme [23–25] (Fig. 1).Fig. 1


Evolutionary relationships between heme-binding ferredoxin α + β barrels.

Acharya G, Kaur G, Subramanian S - BMC Bioinformatics (2016)

Representative structures of the heme-binding ferredoxin α + β barrel superfamily. (a) Ribbon diagram of the structures of OxdA (PDB identifier 3A16), Cld (PDB identifier 3NN1), MhuD (PDB identifier 3HX9), IsdG (PDB identifier 2ZDP), DyP (PDB identifier 3VXJ) and Siroheme decarboxylase (PDB identifier 4UN1). The individual ferredoxin-like folds in all structures have been colored from their N- to C-termini in chainbow coloring scheme of PyMOL and are faded to highlight the position of heme (magenta). Elements that do not constitute a part of the core of the ferredoxin-like fold are colored white. (b) A comparison of heme binding sites using topology diagrams. (c) Orientation of heme-moieties in different proteins of the ferredoxin α + β barrel superfamily. Here, the porphyrin ring of heme and siroheme substituents is shown as a rectangle and the extensions from the rectangle denote the propionate side chains
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig1: Representative structures of the heme-binding ferredoxin α + β barrel superfamily. (a) Ribbon diagram of the structures of OxdA (PDB identifier 3A16), Cld (PDB identifier 3NN1), MhuD (PDB identifier 3HX9), IsdG (PDB identifier 2ZDP), DyP (PDB identifier 3VXJ) and Siroheme decarboxylase (PDB identifier 4UN1). The individual ferredoxin-like folds in all structures have been colored from their N- to C-termini in chainbow coloring scheme of PyMOL and are faded to highlight the position of heme (magenta). Elements that do not constitute a part of the core of the ferredoxin-like fold are colored white. (b) A comparison of heme binding sites using topology diagrams. (c) Orientation of heme-moieties in different proteins of the ferredoxin α + β barrel superfamily. Here, the porphyrin ring of heme and siroheme substituents is shown as a rectangle and the extensions from the rectangle denote the propionate side chains
Mentions: Heme, a metal-porphyrin compound, is associated with at least six different families of this superfamily [2, 10, 12, 13]. Of these, three families, namely, Cld, DyP and aldoxime dehydratase (OxdA, PF13816) have been identified to bind heme as a cofactor [12–14], while IsdG and HemQ bind heme as a substrate and product, respectively [9, 10] (Fig. 1a). For members of the EfeB family, heme has been proposed to play a role in the assimilation of iron [15] and in the extra-cytoplasmic transport of the protein [16]. Heme is seen to bind at two spatially distinct regions in the barrel [2]. IsdG [17], HmoB [18], MhuD [19] and OxdA [14] share similar spatial location of the heme-binding site [2], while Cld [20], DyP [21] and EfeB [22] bind heme at a different location [2]. The exact location of the heme-binding histidine and orientation of the heme moiety vary even among proteins with the similar spatial location of heme [2] (Fig. 1b, c). In addition to these heme-binding families, a recently structurally characterized protein, siroheme decarboxylase, which is a member of the AsnC transcription regulator family, is known to function in the alternative heme biosynthesis pathway in some bacteria and archaea [23, 24]. Siroheme decarboxylase has been shown to bind siroheme, a metabolic intermediate in the alternative heme synthesis pathway, and convert it to didecarboxysiroheme [23–25] (Fig. 1).Fig. 1

Bottom Line: We analyze the heme-binding sites in these proteins as well as their barrel topologies.We examine the heme-binding pockets and explore the versatility of the α + β barrels ability to accommodate heme or heme-related moieties, such as siroheme, in at least three different sites, namely, the mode seen in IsdG/OxdA, Cld/DyP/EfeB/HemQ and siroheme decarboxylase barrels.Our study offers insights into the plausible evolutionary relationships between the two distinct barrel packing topologies and relate the observed heme-binding sites to these topologies.

View Article: PubMed Central - PubMed

Affiliation: CSIR-Institute of Microbial Technology (IMTECH), Sector 39-A, Chandigarh, India.

ABSTRACT

Background: The α + β barrel superfamily of the ferredoxin-like fold consists of a functionally diverse group of evolutionarily related proteins. The barrel architecture of these proteins is formed by either homo-/hetero-dimerization or duplication and fusion of ferredoxin-like domains. Several members of this superfamily bind heme in order to carry out their functions.

Results: We analyze the heme-binding sites in these proteins as well as their barrel topologies. Our comparative structural analysis of these heme-binding barrels reveals two distinct modes of packing of the ferredoxin-like domains to constitute the α + β barrel, which is typified by the Type-1/IsdG-like and Type-2/OxdA-like proteins, respectively. We examine the heme-binding pockets and explore the versatility of the α + β barrels ability to accommodate heme or heme-related moieties, such as siroheme, in at least three different sites, namely, the mode seen in IsdG/OxdA, Cld/DyP/EfeB/HemQ and siroheme decarboxylase barrels.

Conclusions: Our study offers insights into the plausible evolutionary relationships between the two distinct barrel packing topologies and relate the observed heme-binding sites to these topologies.

No MeSH data available.