Nonplanar porphyrins and their biological relevance: Ground and excited state dynamics

Ravikanth, Mangalampalli; Chandrashekar, Tavarekere K.

doi:10.1007/bfb0036827

Cited by 192 publications

(121 citation statements)

References 204 publications

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“…5 Biochemical and structural studies have revealed that heme distortion is correlated to changes in heme reactivity, ligand binding, and protein conformation. 5,14,[18][19][20][21]22,23 As observed in the structure reported here, disconnection of the heme and proximal helix in the H102G mutant results in a significantly relaxed heme cofactor conformation. A comparison of the heme cofactors shows that pyrroles A and D move away from the proximal side of the heme pocket toward the distal side in the H102G mutant compared with wild type [ Fig.…”

Section: Analysis Of the Heme-binding Pocketsupporting

confidence: 76%

Structural insights into the molecular mechanism of H‐NOX activation

et al. 2010

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Nitric oxide (NO) signaling in mammals controls important processes such as smooth muscle relaxation and neurotransmission by the activation of soluble guanylate cyclase (sGC). NO binding to the heme domain of sGC leads to dissociation of the iron-histidine (Fe-His) bond, which is required for enzyme activity. The heme domain of sGC belongs to a larger class of proteins called H-NOX (Heme-Nitric oxide/OXygen) binding domains. Previous crystallographic studies on H-NOX domains demonstrate a correlation between heme bending and protein conformation. It was unclear, however, whether these structural changes were important for signal transduction. Subsequent NMR solution structures of H-NOX proteins show a conformational change upon disconnection of the heme and proximal helix, similar to those observed in the crystallographic studies. The atomic details of these conformational changes, however, are lacking in the NMR structures especially at the heme pocket. Here, a high-resolution crystal structure of an H-NOX mutant mimicking a broken Fe-His bond is reported. This mutant exhibits specific changes in heme conformation and major N-terminal displacements relative to the wild-type H-NOX protein.Fe-His ligation is ubiquitous in all H-NOX domains, and therefore, the heme and protein conformational changes observed in this study are likely to occur throughout the H-NOX family when NO binding leads to rupture of the Fe-His bond.

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Section: Analysis Of the Heme-binding Pocketsupporting

confidence: 76%

Structural insights into the molecular mechanism of H‐NOX activation

et al. 2010

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“…In contrast, the same value for HEC, a structure determined to 1.5-Å resolution, is 0.72 Å. Studies with synthetic hemes have shown that nonplanar heme groups are more easily oxidized than their planar counterparts (28), and the nonplanarity can affect not only the site of oxidation (metal or ring) but also the type of oxidation (two electrons vs. one electron) (29). Because distortion of heme planarity is energetically unfavorable (30), the difference in AOS and catalase heme shape is likely necessary for the difference in redox properties.…”

Section: The Chemical Nature Of the U-shaped Cavity Is Complementary mentioning

confidence: 93%

The structure of coral allene oxide synthase reveals a catalase adapted for metabolism of a fatty acid hydroperoxide

Oldham

Brash

Newcomer

2004

Proc. Natl. Acad. Sci. U.S.A.

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8R-Lipoxygenase and allene oxide synthase (AOS) are parts of a naturally occurring fusion protein from the coral Plexaura homomalla. AOS catalyses the production of an unstable epoxide (an allene oxide) from the fatty acid hydroperoxide generated by the lipoxygenase activity. Here, we report the structure of the AOS domain and its striking structural homology to catalase. Whereas nominal sequence identity between the enzymes had been previously described, the extent of structural homology observed was not anticipated, given that this enzyme activity had been exclusively associated with the P450 superfamily, and conservation of a catalase fold without catalase activity is unprecedented. Whereas the heme environment is largely conserved, the AOS heme is planar and the distal histidine is flanked by two hydrogen-bonding residues. These critical differences likely facilitate the switch from a catalatic activity to that of a fatty acid hydroperoxidase.eicosanoids ͉ heme

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“…45 is also required to complete the story and give a full measure of the key properties that have been affected.…”

Section: Figmentioning

confidence: 99%

“…30,31,45 Throughout the following sections only selected examples of the various approaches that have proved successful will be highlighted in order to illustrate the influence of non-planarity on physicochemical properties. An outline of our own involvement in the field and how it developed over the first two decades was given here in 2006.…”

Section: Model Compounds and Structural Correlationsmentioning

confidence: 99%

Conformational control of cofactors in nature – the influence of protein-induced macrocycle distortion on the biological function of tetrapyrroles

2015

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Tetrapyrrole-containing proteins are one of the most fundamental classes of enzymes in nature and it remains an open question to give a chemical rationale for the multitude of biological reactions that can be catalyzed by these pigmentprotein complexes. There are many fundamental processes where the same (i.e., chemically identical) porphyrin cofactor is involved in chemically quite distinct reactions. For example, heme is the active cofactor for oxygen transport and storage (hemoglobin, myoglobin) and for the incorporation of molecular oxygen in organic substrates (cytochrome P 450 ). It is involved in the terminal oxidation (cytochrome c oxidase) and the metabolism of H 2 O 2 (catalases and peroxidases) and catalyzes various electron transfer reactions in cytochromes. Likewise, in photosynthesis the same chlorophyll cofactor may function as a reaction center pigment (charge separation) or as an accessory pigment (exciton transfer) in light harvesting complexes (e.g., chlorophyll a). Whilst differences in the apoprotein sequences alone cannot explain the often drastic differences in physicochemical properties encountered for the same cofactor in diverse protein complexes, a critical factor for all biological functions must be the close structural interplay between bound cofactors and the respective apoprotein in addition to factors such as hydrogen bonding or electronic effects. Here, we explore how nature can use the same chemical molecule as a cofactor for chemically distinct reactions using the concept of conformational flexibility of tetrapyrroles. The multifaceted roles of tetrapyrroles are discussed in the context of the current knowledge on distorted porphyrins. Contemporary analytical methods now allow a more quantitative look at cofactors in protein complexes and the development of the field is illustrated by case studies on hemeproteins and photosynthetic complexes. Specific tetrapyrrole conformations are now used to prepare bioengineered designer proteins with specific catalytic or photochemical properties.

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Nonplanar porphyrins and their biological relevance: Ground and excited state dynamics

Cited by 192 publications

References 204 publications

Structural insights into the molecular mechanism of H‐NOX activation

Structural insights into the molecular mechanism of H‐NOX activation

The structure of coral allene oxide synthase reveals a catalase adapted for metabolism of a fatty acid hydroperoxide

Conformational control of cofactors in nature – the influence of protein-induced macrocycle distortion on the biological function of tetrapyrroles

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