The Crystal Structure of Synechocystis Hemoglobin with a Covalent Heme Linkage

Hoy, Julie A.; Kundu, Suman; Trent, James T.; Ramaswamy, S.; Hargrove, Mark S.

doi:10.1074/jbc.m313707200

Cited by 74 publications

(87 citation statements)

References 57 publications

(58 reference statements)

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“…1). In contrast, the recently solved crystal structure of hexacoordinated Ss-trHb, where the sixth heme ligand is residue HisE10, 2 did not show evidence of such cavity network, likely related to extensive conformational changes observed in the protein distal site region (8).…”

Section: Truncated Hemoglobins (Trhbs)mentioning

confidence: 54%

“…(Ss-trHb) and one group II trHb from M. tuberculosis (Mt-trHbO) have been structurally characterized (5)(6)(7)(8)(9). The main structural features highlighted by these studies are an unprecedented two-on-two ␣-helical sandwich fold, a ligand-dependent hydrogen-bonding network within the distal heme pocket, and a protein matrix hydrophobic tunnel/cavity network connecting the solvent space to the heme distal pocket through one or two access sites (5,6).…”

Section: Truncated Hemoglobins (Trhbs)mentioning

confidence: 99%

See 1 more Smart Citation

Heme-Ligand Tunneling in Group I Truncated Hemoglobins

Milani

Pesce²,

Ouellet

et al. 2004

Journal of Biological Chemistry

132

221

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Truncated hemoglobins (trHbs) are small hemoproteins forming a separate cluster within the hemoglobin superfamily; their functional roles in bacteria, plants, and unicellular eukaryotes are marginally understood. Crystallographic investigations have shown that the trHb fold (a two-on-two ␣-helical sandwich related to the globin fold) hosts a protein matrix tunnel system offering a potential path for ligand diffusion to the heme distal site. The tunnel topology is conserved in group I trHbs, although with modulation of its size/structure. Here, we present a crystallographic investigation on trHbs from Mycobacterium tuberculosis, Chlamydomonas eugametos, and Paramecium caudatum, showing that treatment of trHb crystals under xenon pressure leads to binding of xenon atoms at specific (conserved) sites along the protein matrix tunnel. The crystallographic results are in keeping with data from molecular dynamics simulations, where a dioxygen molecule is left free to diffuse within the protein matrix. Modulation of xenon binding over four main sites is related to the structural properties of the tunnel system in the three trHbs and may be connected to their functional roles. In a parallel crystallographic investigation on M. tuberculosis trHbN, we show that butyl isocyanide also binds within the apolar tunnel, in excellent agreement with concepts derived from the xenon binding experiments. These results, together with recent data on atypical CO rebinding kinetics to group I trHbs, underline the potential role of the tunnel system in supporting diffusion, but also accumulation in multiple copies, of low polarity ligands/molecules within group I trHbs. Truncated hemoglobins (trHbs)1 are small oxygen-binding hemoproteins, identified in bacteria, higher plants, and in certain unicellular eukaryotes, building a separate cluster within the hemoglobin superfamily. Based on amino acid sequence analysis, three trHb phylogenetic groups (groups I, II, and III) have been recognized (1). TrHbs display amino acid sequences that are 20 -40 residues shorter than (non)vertebrate hemoglobins, to which they are scarcely related by sequence similarity. Notably, trHbs belonging to the different groups, but also within the same group, may share less then 20% amino acid sequence identity (1) (Fig. 1). TrHbs from more than one group can coexist in some bacteria, suggesting a wide diversification of functions. Possible trHb functions that are consistent with observed biophysical properties include long term ligand or substrate storage, NO detoxification, O 2 /NO sensor, redox reactions, and O 2 delivery under hypoxic conditions (1-3). In Mycobacterium bovis BCG, trHbN promotes an efficient dioxygenase reaction whereby NO is converted to nitrate by the oxygenated heme (4).So far, four group I trHbs from Chlamydomonas eugametos (Ce-trHb), Paramecium caudatum (Pc-trHb), Mycobacterium tuberculosis (Mt-trHbN), and Synechocystis sp. (Ss-trHb) and one group II trHb from M. tuberculosis (Mt-trHbO) have been structurally characterized (5-9). The main s...

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Section: Truncated Hemoglobins (Trhbs)mentioning

confidence: 54%

Section: Truncated Hemoglobins (Trhbs)mentioning

confidence: 99%

Heme-Ligand Tunneling in Group I Truncated Hemoglobins

Milani

Pesce²,

Ouellet

et al. 2004

Journal of Biological Chemistry

132

221

View full text Add to dashboard Cite

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“…The hexacoordinate Synechocystis sp. 2/2HbN displays a covalent bond linking HisH16 and the 2-vinyl group of the heme, that may modulate the reactivity of the heme group (10,11,21,22). Moreover, heme isomerism has been reported in some of the 2/2Hb crystal structures (23).…”

Section: Heme Proximal Site In 2/2hbsmentioning

confidence: 99%

Protein structure in the truncated (2/2) hemoglobin family

Pesce¹,

Nardini

Milani

et al. 2007

IUBMB Life

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The discovery of protein sequences belonging to the widespread 'truncated hemoglobin' family has been followed in the last few years by extensive analyses of their three‐dimensional structures. Truncated hemoglobins can be classified in three main groups, in light of their overall structural properties. The three groups adopt a 2‐on‐2 α‐helical sandwich fold, based on four main α‐helices of the classical 3‐on‐3 α‐helical sandwich found in vertebrate and invertebrate globins. Each of the three groups displays sequence and structure specific features. Among these, a protein matrix tunnel system is typical of group I, a Trp residue at the G8 topological site is conserved in groups II and III, and residue TyrB10 is almost invariant in the three groups. Despite sequence variability in the heme distal site region, a strongly intertwined, but varied, network of hydrogen bonds stabilizes the heme ligand in the three protein groups. Fine mechanisms of ligand recognition and stabilization may vary based on group‐specific distal site residues and on differing ligand diffusion pathways to the heme. Taken together, the structural considerations here presented underline that 'truncated hemoglobins' result from careful editing of the 3‐on‐3 α‐helical globin sandwich fold, rather than from simple 'truncation' events. Thus, '2/2Hb' appears the most proper term to concisely address this protein family.

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“…Other examples of unexpected haem-protein links have also come to light. These include the CYP4 family of cytochrome P450s, which contain ester links between the 5-methyl group and a glutamate residue [2][3][4], cyanobacterial haemoglobin, which contains a covalent link between the 2-vinyl group and a histidine residue [5], and the haem chaperone CcmE, which uses a different vinyl-histidine covalent link [6,7].…”

Section: Introductionmentioning

confidence: 99%

Tuning the formation of a covalent haem–protein link by selection of reductive or oxidative conditions as exemplified by ascorbate peroxidase

Metcalfe

Daltrop

Ferguson

et al. 2007

Biochemical Journal

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Raven (2004) J. Am. Chem. Soc. 126, [16242][16243][16244][16245][16246][16247][16248] has shown that the introduction of a methionine residue (S160M variant) close to the 2-vinyl group of the haem in ascorbate peroxidase leads to the formation of a covalent haem-methionine linkage under oxidative conditions (i.e. on reaction with H 2 O 2 ). In the present study, spectroscopic, HPLC and mass spectrometric evidence is presented to show that covalent attachment of the haem to an engineered cysteine residue can also occur in the S160C variant, but, in this case, under reducing conditions analogous to those used in the formation of covalent links in cytochrome c. The data add an extra dimension to our understanding of haem to protein covalent bond formation because they show that different types of covalent attachment (one requiring an oxidative mechanism, the other a reductive pathway) are both accessible within same protein architecture.

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The Crystal Structure of Synechocystis Hemoglobin with a Covalent Heme Linkage

Cited by 74 publications

References 57 publications

Heme-Ligand Tunneling in Group I Truncated Hemoglobins

Heme-Ligand Tunneling in Group I Truncated Hemoglobins

Protein structure in the truncated (2/2) hemoglobin family

Tuning the formation of a covalent haem–protein link by selection of reductive or oxidative conditions as exemplified by ascorbate peroxidase

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