Limits...
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.


Related in: MedlinePlus

Structural and sequence features of the heme-binding region in IsdG-like, OxdA, Cld/Dyp/EfeB/HemQ, and siroheme decarboxylase proteins. (a) Structure superimposition stereo diagram of the Cα backbone of IsdG-like ferredoxin-like monomer (PDB identifier 2ZDP; cyan), the C-terminal domain of OxdA-like (PDB identifier 3A16_A; red) and the C-terminal domain of Cld/DyP/EfeB/HemQ-like (PDB identifier 3NN1_A; green). (b) Stereo diagram of a ferredoxin-like domain of siroheme decarboxylase (PDB identifier 4UN1_A). In panels (a, b), heme and side chain of the heme-binding histidine is shown in stick form. c Structure-based MSA of IsdG, OxdA, Cld/Dyp/EfeB/HemQ and siroheme decarboxylase. PDB identifier/UniProt ID, organism name, start, and end for each sequence are mentioned. The region of circular permutation is indicated by ‘/’ and the sequence number around this region is colored red. The secondary structure diagram for a ferredoxin-like domain is indicated above the alignment, where arrows represent β-strands and rectangles indicate α-helices. The number of omitted residues for large insertions is boxed in green. The sequence region(s) corresponding to disorder in structure or structurally not superimposable regions is italicized. Organism abbreviations: Sa-Staphylococcus aureus, Mt-Mycobacterium tuberculosis, Bs-Bacillus subtilis, Bc-Bacillus cereus, Dr-Deinococcus radiodurans, Bt-Bacteroides thetaiotaomicron, Ap-Acetobacter pasteurianus, Aa-Alicyclobacillus acidocaldarius, Te-Taylorella equigenitalis, Cn-Candidatus nitrosoarchaeum, Al-Acholeplasma laidlawii, Bp-Beggiatoa sp., Sc-Streptococcus criceti, Er-Erysipelothrix rhusiopathiae, Ss-Staphylococcus saprophyticus, Ns-Novosphingobium sp., Kr-Ktedonobacter racemifer, Mu-Methyloversatilis universalis, At-Agrobacterium tumefaciens, Bm-Burkholderia multivorans, Sp-Streptomyces sp., Re-Rhodococcus erythropolis, Sw-Shewanella woodyi, Sl-Streptomyces albus, Am-Actinosynnema mirum, Vd-Verticillium dahliae, Vp-Variovorax paradoxus, Ko-Klebsiella oxytoca, Pm-Patulibacter medicamentivorans, Gf-Gibberella fujikuroi, Fo-Fusarium oxysporum, Pd-Penicillium digitatum, Bf-Botryotinia fuckeliana, Nf-Neosartorya fischeri, Nw-Nitrobacter winogradskyi, Tt-Thermus thermophilus, Ci-Candidatus Nitrospira, So-Shewanella oneidensis, Ba-Bjerkandera adusta, Ec-Escherichia coli, Dd-Desulfovibrio desulfuricans, Ht-Hydrogenobacter thermophilus
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4835899&req=5

Fig3: Structural and sequence features of the heme-binding region in IsdG-like, OxdA, Cld/Dyp/EfeB/HemQ, and siroheme decarboxylase proteins. (a) Structure superimposition stereo diagram of the Cα backbone of IsdG-like ferredoxin-like monomer (PDB identifier 2ZDP; cyan), the C-terminal domain of OxdA-like (PDB identifier 3A16_A; red) and the C-terminal domain of Cld/DyP/EfeB/HemQ-like (PDB identifier 3NN1_A; green). (b) Stereo diagram of a ferredoxin-like domain of siroheme decarboxylase (PDB identifier 4UN1_A). In panels (a, b), heme and side chain of the heme-binding histidine is shown in stick form. c Structure-based MSA of IsdG, OxdA, Cld/Dyp/EfeB/HemQ and siroheme decarboxylase. PDB identifier/UniProt ID, organism name, start, and end for each sequence are mentioned. The region of circular permutation is indicated by ‘/’ and the sequence number around this region is colored red. The secondary structure diagram for a ferredoxin-like domain is indicated above the alignment, where arrows represent β-strands and rectangles indicate α-helices. The number of omitted residues for large insertions is boxed in green. The sequence region(s) corresponding to disorder in structure or structurally not superimposable regions is italicized. Organism abbreviations: Sa-Staphylococcus aureus, Mt-Mycobacterium tuberculosis, Bs-Bacillus subtilis, Bc-Bacillus cereus, Dr-Deinococcus radiodurans, Bt-Bacteroides thetaiotaomicron, Ap-Acetobacter pasteurianus, Aa-Alicyclobacillus acidocaldarius, Te-Taylorella equigenitalis, Cn-Candidatus nitrosoarchaeum, Al-Acholeplasma laidlawii, Bp-Beggiatoa sp., Sc-Streptococcus criceti, Er-Erysipelothrix rhusiopathiae, Ss-Staphylococcus saprophyticus, Ns-Novosphingobium sp., Kr-Ktedonobacter racemifer, Mu-Methyloversatilis universalis, At-Agrobacterium tumefaciens, Bm-Burkholderia multivorans, Sp-Streptomyces sp., Re-Rhodococcus erythropolis, Sw-Shewanella woodyi, Sl-Streptomyces albus, Am-Actinosynnema mirum, Vd-Verticillium dahliae, Vp-Variovorax paradoxus, Ko-Klebsiella oxytoca, Pm-Patulibacter medicamentivorans, Gf-Gibberella fujikuroi, Fo-Fusarium oxysporum, Pd-Penicillium digitatum, Bf-Botryotinia fuckeliana, Nf-Neosartorya fischeri, Nw-Nitrobacter winogradskyi, Tt-Thermus thermophilus, Ci-Candidatus Nitrospira, So-Shewanella oneidensis, Ba-Bjerkandera adusta, Ec-Escherichia coli, Dd-Desulfovibrio desulfuricans, Ht-Hydrogenobacter thermophilus

Mentions: Although non-identical, the two barrel packing modes may be rationalized by rotating one of the ferredoxin-like domains in Type-1 proteins by 1800, which would result in a Type-2 packing (Fig. 2). The ferredoxin-like domain possesses internal symmetry, which allows us to superimpose two such domains even after rotating them with respect to each other, as in either case, i.e. with or without rotation, we align similarly arranged symmetric β-α-β repeats. The rotation of one of the domains of IsdG with respect to OxdA further allows us to rationalize the different locations of the heme-binding-histidine in IsdG and OxdA-like proteins (Fig. 2). Studies have revealed the presence of two heme-binding active sites, one in the cleft of each ferredoxin-like domain of the barrel in IsdG and IsdI [32]. The heme-degrading catalytic triad is made up of Asn6, Trp66, and His76 residues, where the Trp residue is implicated in ruffling of the heme moiety [32, 33]. In the structure of OxdA from Rhodococcus sp., which has two ferredoxin-like domains joined by a linker region and additional secondary structural elements, a single heme-binding site is present in the cleft of the C-terminal ferredoxin-like domain of the barrel [14]. The apo- and holo-structures of OxdA reveal His299 as the proximal residue for heme and two functionally-important distal residues, Ser219 and His320 [14], which help in orienting the heme-bound substrate for the catalytic elimination of OH group of aldoxime [34, 35]. A comparison of the heme-binding domains of IsdG and OxdA reveals significant sequence as well as structure similarity around the heme-binding site (Fig. 3, Additional file 1: Figure S1). For a detailed comparison of protein-heme interactions, the readers may refer to Celis and DuBois, 2015 [2]. Heme is bound at a similar spatial location in IsdG and OxdA barrels [2] and the heme-binding histidine is contributed by the α2 of the individual ferredoxin-like domains [14, 32]. However, the histidine contributing α-helix is not topologically equivalent (Fig. 2), as in OxdA, heme is bound on α4 of the barrel which is topologically equivalent to the α1, and not the heme-binding α2, of the ferredoxin-like domain in the IsdG barrel (Table 2, Fig. 2a). Thus, an 1800 rotation of the C-terminal domain of IsdG not only helps rationalize the barrel packing-modes but also helps correctly superimpose the heme-binding α-helices of IsdG and OxdA.Fig. 3


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

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

Structural and sequence features of the heme-binding region in IsdG-like, OxdA, Cld/Dyp/EfeB/HemQ, and siroheme decarboxylase proteins. (a) Structure superimposition stereo diagram of the Cα backbone of IsdG-like ferredoxin-like monomer (PDB identifier 2ZDP; cyan), the C-terminal domain of OxdA-like (PDB identifier 3A16_A; red) and the C-terminal domain of Cld/DyP/EfeB/HemQ-like (PDB identifier 3NN1_A; green). (b) Stereo diagram of a ferredoxin-like domain of siroheme decarboxylase (PDB identifier 4UN1_A). In panels (a, b), heme and side chain of the heme-binding histidine is shown in stick form. c Structure-based MSA of IsdG, OxdA, Cld/Dyp/EfeB/HemQ and siroheme decarboxylase. PDB identifier/UniProt ID, organism name, start, and end for each sequence are mentioned. The region of circular permutation is indicated by ‘/’ and the sequence number around this region is colored red. The secondary structure diagram for a ferredoxin-like domain is indicated above the alignment, where arrows represent β-strands and rectangles indicate α-helices. The number of omitted residues for large insertions is boxed in green. The sequence region(s) corresponding to disorder in structure or structurally not superimposable regions is italicized. Organism abbreviations: Sa-Staphylococcus aureus, Mt-Mycobacterium tuberculosis, Bs-Bacillus subtilis, Bc-Bacillus cereus, Dr-Deinococcus radiodurans, Bt-Bacteroides thetaiotaomicron, Ap-Acetobacter pasteurianus, Aa-Alicyclobacillus acidocaldarius, Te-Taylorella equigenitalis, Cn-Candidatus nitrosoarchaeum, Al-Acholeplasma laidlawii, Bp-Beggiatoa sp., Sc-Streptococcus criceti, Er-Erysipelothrix rhusiopathiae, Ss-Staphylococcus saprophyticus, Ns-Novosphingobium sp., Kr-Ktedonobacter racemifer, Mu-Methyloversatilis universalis, At-Agrobacterium tumefaciens, Bm-Burkholderia multivorans, Sp-Streptomyces sp., Re-Rhodococcus erythropolis, Sw-Shewanella woodyi, Sl-Streptomyces albus, Am-Actinosynnema mirum, Vd-Verticillium dahliae, Vp-Variovorax paradoxus, Ko-Klebsiella oxytoca, Pm-Patulibacter medicamentivorans, Gf-Gibberella fujikuroi, Fo-Fusarium oxysporum, Pd-Penicillium digitatum, Bf-Botryotinia fuckeliana, Nf-Neosartorya fischeri, Nw-Nitrobacter winogradskyi, Tt-Thermus thermophilus, Ci-Candidatus Nitrospira, So-Shewanella oneidensis, Ba-Bjerkandera adusta, Ec-Escherichia coli, Dd-Desulfovibrio desulfuricans, Ht-Hydrogenobacter thermophilus
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4835899&req=5

Fig3: Structural and sequence features of the heme-binding region in IsdG-like, OxdA, Cld/Dyp/EfeB/HemQ, and siroheme decarboxylase proteins. (a) Structure superimposition stereo diagram of the Cα backbone of IsdG-like ferredoxin-like monomer (PDB identifier 2ZDP; cyan), the C-terminal domain of OxdA-like (PDB identifier 3A16_A; red) and the C-terminal domain of Cld/DyP/EfeB/HemQ-like (PDB identifier 3NN1_A; green). (b) Stereo diagram of a ferredoxin-like domain of siroheme decarboxylase (PDB identifier 4UN1_A). In panels (a, b), heme and side chain of the heme-binding histidine is shown in stick form. c Structure-based MSA of IsdG, OxdA, Cld/Dyp/EfeB/HemQ and siroheme decarboxylase. PDB identifier/UniProt ID, organism name, start, and end for each sequence are mentioned. The region of circular permutation is indicated by ‘/’ and the sequence number around this region is colored red. The secondary structure diagram for a ferredoxin-like domain is indicated above the alignment, where arrows represent β-strands and rectangles indicate α-helices. The number of omitted residues for large insertions is boxed in green. The sequence region(s) corresponding to disorder in structure or structurally not superimposable regions is italicized. Organism abbreviations: Sa-Staphylococcus aureus, Mt-Mycobacterium tuberculosis, Bs-Bacillus subtilis, Bc-Bacillus cereus, Dr-Deinococcus radiodurans, Bt-Bacteroides thetaiotaomicron, Ap-Acetobacter pasteurianus, Aa-Alicyclobacillus acidocaldarius, Te-Taylorella equigenitalis, Cn-Candidatus nitrosoarchaeum, Al-Acholeplasma laidlawii, Bp-Beggiatoa sp., Sc-Streptococcus criceti, Er-Erysipelothrix rhusiopathiae, Ss-Staphylococcus saprophyticus, Ns-Novosphingobium sp., Kr-Ktedonobacter racemifer, Mu-Methyloversatilis universalis, At-Agrobacterium tumefaciens, Bm-Burkholderia multivorans, Sp-Streptomyces sp., Re-Rhodococcus erythropolis, Sw-Shewanella woodyi, Sl-Streptomyces albus, Am-Actinosynnema mirum, Vd-Verticillium dahliae, Vp-Variovorax paradoxus, Ko-Klebsiella oxytoca, Pm-Patulibacter medicamentivorans, Gf-Gibberella fujikuroi, Fo-Fusarium oxysporum, Pd-Penicillium digitatum, Bf-Botryotinia fuckeliana, Nf-Neosartorya fischeri, Nw-Nitrobacter winogradskyi, Tt-Thermus thermophilus, Ci-Candidatus Nitrospira, So-Shewanella oneidensis, Ba-Bjerkandera adusta, Ec-Escherichia coli, Dd-Desulfovibrio desulfuricans, Ht-Hydrogenobacter thermophilus
Mentions: Although non-identical, the two barrel packing modes may be rationalized by rotating one of the ferredoxin-like domains in Type-1 proteins by 1800, which would result in a Type-2 packing (Fig. 2). The ferredoxin-like domain possesses internal symmetry, which allows us to superimpose two such domains even after rotating them with respect to each other, as in either case, i.e. with or without rotation, we align similarly arranged symmetric β-α-β repeats. The rotation of one of the domains of IsdG with respect to OxdA further allows us to rationalize the different locations of the heme-binding-histidine in IsdG and OxdA-like proteins (Fig. 2). Studies have revealed the presence of two heme-binding active sites, one in the cleft of each ferredoxin-like domain of the barrel in IsdG and IsdI [32]. The heme-degrading catalytic triad is made up of Asn6, Trp66, and His76 residues, where the Trp residue is implicated in ruffling of the heme moiety [32, 33]. In the structure of OxdA from Rhodococcus sp., which has two ferredoxin-like domains joined by a linker region and additional secondary structural elements, a single heme-binding site is present in the cleft of the C-terminal ferredoxin-like domain of the barrel [14]. The apo- and holo-structures of OxdA reveal His299 as the proximal residue for heme and two functionally-important distal residues, Ser219 and His320 [14], which help in orienting the heme-bound substrate for the catalytic elimination of OH group of aldoxime [34, 35]. A comparison of the heme-binding domains of IsdG and OxdA reveals significant sequence as well as structure similarity around the heme-binding site (Fig. 3, Additional file 1: Figure S1). For a detailed comparison of protein-heme interactions, the readers may refer to Celis and DuBois, 2015 [2]. Heme is bound at a similar spatial location in IsdG and OxdA barrels [2] and the heme-binding histidine is contributed by the α2 of the individual ferredoxin-like domains [14, 32]. However, the histidine contributing α-helix is not topologically equivalent (Fig. 2), as in OxdA, heme is bound on α4 of the barrel which is topologically equivalent to the α1, and not the heme-binding α2, of the ferredoxin-like domain in the IsdG barrel (Table 2, Fig. 2a). Thus, an 1800 rotation of the C-terminal domain of IsdG not only helps rationalize the barrel packing-modes but also helps correctly superimpose the heme-binding α-helices of IsdG and OxdA.Fig. 3

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.


Related in: MedlinePlus