pH-dependent structural changes in haemoglobin component V from the midge larva<i>Propsilocerus akamusi</i>(Orthocladiinae, Diptera)

Kuwada, Takao; Hasegawa, Tomokazu; Takagi, Takashi; Sato, Isamu; Shishikura, Fumio

doi:10.1107/s0907444909055760

Cited by 6 publications

(3 citation statements)

References 54 publications

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“…Stable O 2 binding has not been reported for other hemophores, although CO‐adducts of the HasA hemophore (Lukat‐Rodgers, Rodgers, Caillet‐Saguy, Izadi‐Pruneyre, & Lecroisey, ; Ozaki et al, ) and IsdA (Vermeiren, Pluym, Mack, Heinrichs, & Stillman, ) have been described. Hemophilin has two appropriately positioned residues, Gln74 and Arg82, that are capable of hydrogen bonding to O 2 or CO, as has been observed in globin (Cutruzzola, Travaglini Allocatelli, Brancaccio, & Brunori, ; Kuwada, Hasegawa, Takagi, Sato, & Shishikura, ; Rohlfs et al, ; Yang, Kloek, Goldberg, & Mathews, ) and non‐globin proteins (Gong, Hao, & Chan, ; Ishitsuka et al, ). In addition, arginine is expected to play a role in stabilising anionic ligands bound to ferric heme (Bolognesi et al, , ; Conti et al, ; Cutruzzola et al, ).…”

Section: Discussionmentioning

confidence: 88%

A heme‐binding protein produced by Haemophilus haemolyticus inhibits non‐typeable Haemophilus influenzae

Latham

Torrado

Atto

et al. 2019

Molecular Microbiology

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Commensal bacteria serve as an important line of defense against colonisation by opportunisitic pathogens, but the underlying molecular mechanisms remain poorly explored. Here, we show that strains of a commensal bacterium, Haemophilus haemolyticus, make hemophilin, a heme‐binding protein that inhibits growth of the opportunistic pathogen, non‐typeable Haemophilus influenzae (NTHi) in culture. We purified the NTHi‐inhibitory protein from H. haemolyticus and identified the hemophilin gene using proteomics and a gene knockout. An x‐ray crystal structure of recombinant hemophilin shows that the protein does not belong to any of the known heme‐binding protein folds, suggesting that it evolved independently. Biochemical characterisation shows that heme can be captured in the ferrous or ferric state, and with a variety of small heme‐ligands bound, suggesting that hemophilin could function under a range of physiological conditions. Hemophilin knockout bacteria show a limited capacity to utilise free heme for growth. Our data suggest that hemophilin is a hemophore and that inhibition of NTHi occurs by heme starvation, raising the possibility that competition from hemophilin‐producing H. haemolyticus could antagonise NTHi colonisation in the respiratory tract.

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Section: Discussionmentioning

confidence: 88%

A heme‐binding protein produced by Haemophilus haemolyticus inhibits non‐typeable Haemophilus influenzae

Latham

Torrado

Atto

et al. 2019

Molecular Microbiology

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“…Figure 3A-3 shows that the Ca tracing of the two models overlapped comparably (least square fitting using Ca atoms), indicating the overall structural differences detected in their helices. We are now investigating pH-dependent conformational changes of crystals under other pH conditions, including the two pH conditions performed in this study, as examined in our previous report (24). Comparisons of the tertiary and quaternary structures of Podocnemis Hb A (form A) with those of Anser Hb A as well as those of human Hb A are shown in Table 2 and Figs.…”

Section: Primary Structures Of a A -And B-globinsmentioning

confidence: 91%

Side‐necked turtle (Pleurodira, Chelonia, reptilia) hemoglobin: cDNA‐derived primary structures and X‐ray crystal structures of Hb A

2011

Self Cite

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Red blood cells of yellow-spotted river turtles (Podocnemis unifilis, Pleurodira, Chelonia, REPTILIA) have two hemoglobin (Hb) components, Hb A and Hb D. We purified the hemoglobin component homologous to amniote (reptiles, birds, and mammals) adult Hb A which comprises two identical α(A) -globin polypeptides and two identical β-globin polypeptides. To establish the crystal structure of Podocnemis Hb A, we first determined the globin primary structures using cDNA nucleotide sequencing with the assistance of protein sequencing. The purified Podocnemis Hb A produced a different form of crystal for each of the two different buffer systems used: form A, tetragonal crystals (space group, P4₁2₁2), produced under neutral pH (pH 7-8) conditions; and form B, hexagonal crystals (space group, P6₁22), produced under high alkaline pH (pH 11-13) conditions. Single crystals of the two forms were examined by Raman microscopy with an excitation of 532 nm, indicating their structural differences. The crystal structures of the two forms were constructed by X-ray crystallographic diffraction at a resolution of 2.20 Å for form A and 2.35 Å for form B. The differences of the tertiary and quaternary structures of the two forms were marginal; however, one clear difference was found in helix structure. When comparing Podocnemis Hb A with Hb A from specimens in other taxa, such as Anser indicus (birds) and Homo sapiens (mammals) by SHELXPRO, the root mean square deviation (RMSD) between the corresponding Cα atoms of the two globins does not exceed 2.0 Å. These low values indicate the crystal structures resemble each other. Our data on X-ray crystal structures and Raman spectra not only reveal the first findings on the two crystal forms of Podocnemis unifilis Hb A but also provide the first refined models for reptilian adult Hb A.

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“…Stacking of salt bridges with arenes has been observed in a number of biological contexts. − For instance, cation–anion–aromatic triads are commonly observed at protein–protein interfaces . This can be seen in the interaction of an importin β transport receptor with the GTP-binding protein Ran and in the binding of HIV-1 Nef with the SH3 domain of Src kinases .…”

Section: Introductionmentioning

confidence: 99%

Tuning Stacking Interactions between Asp–Arg Salt Bridges and Heterocyclic Drug Fragments

Bootsma

Wheeler

2018

J. Chem. Inf. Model.

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Stacking interactions can play an integral role in the strength and selectivity of protein–drug binding and are of particular interest given the ubiquity and variety of heterocyclic fragments in drugs. In addition to traditional stacking interactions between aromatic rings, stacking interactions involving heterocyclic drug fragments and protein salt bridges have also been observed. These “salt-bridge stacking interactions” can be quite strong but are not well understood. We studied stacked dimers of the acetate···guanidinium ion pair with a diverse set of 63 heterocycles using robust ab initio methods. The computed interaction energies span more than 10 kcal mol–1, indicating the sensitivity of these salt-bridge stacking interactions to heterocycle features. Trends in both the strength and preferred geometry of these interactions can be understood through analyses of the electrostatic potentials and electric fields above the heterocycles. We have developed new heterocycle descriptors that quantify these effects and used them to create robust predictors of the strength of salt-bridge stacking interactions both in the gas phase and a protein-like dielectric environment. These predictive tools, combined with a set of qualitative guidelines, should facilitate the choice of heterocycles that maximize salt-bridge stacking interactions in drug binding sites.

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pH-dependent structural changes in haemoglobin component V from the midge larvaPropsilocerus akamusi(Orthocladiinae, Diptera)

Cited by 6 publications

References 54 publications

A heme‐binding protein produced by Haemophilus haemolyticus inhibits non‐typeable Haemophilus influenzae

A heme‐binding protein produced by Haemophilus haemolyticus inhibits non‐typeable Haemophilus influenzae

Side‐necked turtle (Pleurodira, Chelonia, reptilia) hemoglobin: cDNA‐derived primary structures and X‐ray crystal structures of Hb A

Tuning Stacking Interactions between Asp–Arg Salt Bridges and Heterocyclic Drug Fragments

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