Crystal Structure of the Visual Chromophores, 11-cis and all-trans Retinal

Gilardi, Richard; Karle, Isabella L.; Karle, J.; Sperling, W.

doi:10.1038/232187c0

Cited by 96 publications

(36 citation statements)

References 16 publications

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“…The bond angles and bond lengths of retinal, which were used in this refinement, differ slightly from those previously used (7). They were taken from Cambridge Structural Database entry cretal10 (47). XtalView (48) was used for the model building stages.…”

Section: Refinement Of the Rhodopsin Structurementioning

confidence: 99%

Advances in Determination of a High-Resolution Three-Dimensional Structure of Rhodopsin, a Model of G-Protein-Coupled Receptors (GPCRs)^,

et al. 2001

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Membrane proteins, encoded by ~20% of genes in almost all organisms, including humans, are critical for cellular communication, electrical and ion balances, structural integrity of the cells and their adhesions, and other functions. Atomic-resolution structures of these proteins furnish important information for understanding their molecular organization and constitute major breakthroughs in our understanding of how they participate in physiological processes. However, obtaining structural information about these proteins has progressed slowly (1,2), mostly because of technical difficulties in the purification and handling of integral membrane proteins. Instability of the proteins in environments lacking phospholipids, the tendency for them to aggregate and precipitate, and/or difficulties with highly heterogeneous preparations of these proteins isolated from heterologous expression systems have hindered application of standard structure determination techniques to these molecules.Among membrane proteins, G-protein-coupled receptors (GPCRs) 1 are of special importance because they form one of the largest and most diverse groups of receptor proteins. More than 400 nonsensory receptors identified in the human genome are involved in the regulation of virtually all physiological processes. Drug addiction, mood control, and memory (via 5-HT6 or neuropeptide receptors) are just a short list of processes in which GPCRs are critically implicated. Another even larger group of GPCRs consist of sensory receptors involved in the fundamental process of translation of light energy (rhodopsin and cone pigments), the detection † This research was supported by NIH Grant EY-09339, awards from Research to Prevent Blindness, Inc. (RPB) SUPPORTING INFORMATION AVAILABLE Tabular listing of the following topics: tilt of the helices, bends within helices, possible hydrogen bonds between helices, closest atoms to the 11-cis-retinal, retinal atoms closest to these protein atoms, and torsion angles for the chromophore. This material is available free of charge via the Internet at http://pubs.acs.org. 1 Abbreviations: GPCR, G-protein-coupled receptor; MAN, β-D-mannose; NAG, 2-N-acetyl-β-D-glucose; BNG, β-nonylglucoside; |F o |, observed structure factor; |F c |, calculated structure factor. R = ∑||F o | − |F c ||/∑|F o |. R cryst is the value for the working set of |F o |, while R free is that calculated for the 5% of reflections set aside for cross validation., NIH Public Access Author ManuscriptBiochemistry. Author manuscript; available in PMC 2006 December 14. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript of chemoattractant molecules, or the detection of compounds stimulating the taste buds (3,4). The activity of GPCRs comes about when binding of diffusable extracellular ligands causes them to switch from quiescent forms to an active conformation capable of interaction with hundreds of G-proteins. Their roles as extracellular ligand-binding proteins make them attractive targets for drug design. GPCRs account ...

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Section: Refinement Of the Rhodopsin Structurementioning

confidence: 99%

Advances in Determination of a High-Resolution Three-Dimensional Structure of Rhodopsin, a Model of G-Protein-Coupled Receptors (GPCRs)^,

et al. 2001

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“…Crystal structures of the visual chromophores 11-cis retinal and all-trans retinal (7), and of eight other carotenoid and xanthenoid derivatives are available (8)(9)(10)(11)(12)(13)(14)(15). The chemical structures and atomic numbering of these compounds are given in Fig.…”

Section: Structural Analysismentioning

confidence: 99%

Structures of the Visual Chromophores and Related Pigments: A Conformational Basis of Visual Excitation

Sundaralingam

Beddell

1972

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

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“…However, a conformational search of 4 and 5 using molecular mechanic calculations (see Figure 3 below) revealed that the polyene side chain is folded in a manner similar to that adopted in the crystal structure of free and opsin-bound 11-cis-retinal. [6,32] As expected, the absorption spectra of analogues 4 and 5 (Table 1) do not significantly differ from that of 1; a small blue-shift (around 12 nm) is observed for the more substituted 4. Therefore, on the assumption that the conjugated polyene structure is close to that of 1, the retinals 4 and 5 fail to form pigments because of enhanced ligand±protein steric interactions.…”

mentioning

confidence: 49%

(9Z)‐ and (11Z)‐8‐Methylretinals for Artificial Visual Pigment Studies: Stereoselective Synthesis, Structure, and Binding Models

Álvarez

Domínguez

Pazos

et al. 2003

Chemistry A European J

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Artificial visual pigment formation was studied by using 8-methyl-substituted retinals in an effort to understand the effect that alkyl substitution of the chromophore side chain has on the visual cycle. The stereoselective synthesis of the 9-cis and 11-cis isomers of 8-methylretinal, as well as the 5-demethylated analogues is also described. The key bond formations consist of a thallium-accelerated Suzuki cross-coupling reaction between cyclohexenylboronic acids and dienyliodides (C6-C7), and a highly stereocontrolled Horner-Wadsworth-Emmons or Wittig condensation (C11-C12). The cyclohexenylboronic acid was prepared by trapping the precursor cyclohexenyllithium species with B(OiPr)(3) or B(OMe)(3). The cyclohexenyllithium species is itself obtained by nBuLi-induced elimination of a trisylhydrazone (Shapiro reaction), or depending upon the steric hindrance of the ring, by iodine-metal exchange. In binding experiments with the apoprotein opsin, only 9-cis-5-demethyl-8-methylretinal yielded an artificial pigment; 9-cis-8-methylretinal simply provided residual binding, while evidence of artificial pigment formation was not found for the 11-cis analogues. Molecular-mechanics-based docking simulations with the crystal structure of rhodopsin have allowed us to rationalize the lack of binding displayed by the 11-cis analogues. Our results indicate that these isomers are highly strained, especially when bound, due to steric clashes with the receptor, and that these interactions are undoubtedly alleviated when 9-cis-5-demethyl-8-methylretinal binds opsin.

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Crystal Structure of the Visual Chromophores, 11-cis and all-trans Retinal

Cited by 96 publications

References 16 publications

Advances in Determination of a High-Resolution Three-Dimensional Structure of Rhodopsin, a Model of G-Protein-Coupled Receptors (GPCRs)^,

Advances in Determination of a High-Resolution Three-Dimensional Structure of Rhodopsin, a Model of G-Protein-Coupled Receptors (GPCRs)^,

Structures of the Visual Chromophores and Related Pigments: A Conformational Basis of Visual Excitation

(9Z)‐ and (11Z)‐8‐Methylretinals for Artificial Visual Pigment Studies: Stereoselective Synthesis, Structure, and Binding Models

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Crystal Structure of the Visual Chromophores, 11-cis and all-trans Retinal

Cited by 96 publications

References 16 publications

Advances in Determination of a High-Resolution Three-Dimensional Structure of Rhodopsin, a Model of G-Protein-Coupled Receptors (GPCRs),

Advances in Determination of a High-Resolution Three-Dimensional Structure of Rhodopsin, a Model of G-Protein-Coupled Receptors (GPCRs),

Structures of the Visual Chromophores and Related Pigments: A Conformational Basis of Visual Excitation

(9Z)‐ and (11Z)‐8‐Methylretinals for Artificial Visual Pigment Studies: Stereoselective Synthesis, Structure, and Binding Models

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Advances in Determination of a High-Resolution Three-Dimensional Structure of Rhodopsin, a Model of G-Protein-Coupled Receptors (GPCRs)^,

Advances in Determination of a High-Resolution Three-Dimensional Structure of Rhodopsin, a Model of G-Protein-Coupled Receptors (GPCRs)^,