Comparing anisotropic displacement parameters in protein structures

Merritt, E.A.

doi:10.1107/s0907444999011853

Cited by 56 publications

(67 citation statements)

References 11 publications

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“…The anisotropy of individual atoms, defined as the ratio of the minimum and maximum eigenvectors of the anisotropic displacement parameter matrix (52), as well as the anisotropy mean values for the protein structures were calculated using PARVATI (53) and ANISOANL (47) validation tools.…”

Section: Calculations Of Average Crystallographic B-factors and Distrmentioning

confidence: 99%

Ligand Binding Induces Conformational Changes in Human Cellular Retinol-binding Protein 1 (CRBP1) Revealed by Atomic Resolution Crystal Structures

Silvaroli¹,

Arne²,

Chełstowska

et al. 2016

Journal of Biological Chemistry

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Important in regulating the uptake, storage, and metabolism of retinoids, cellular retinol-binding protein 1 (CRBP1) is essential for trafficking vitamin A through the cytoplasm. However, the molecular details of ligand uptake and targeted release by CRBP1 remain unclear. Here we report the first structure of CRBP1 in a ligand-free form as well as ultra-high resolution structures of this protein bound to either all-trans-retinol or retinylamine, the latter a therapeutic retinoid that prevents light-induced retinal degeneration. Superpositioning of human apo-and holo-CRBP1 revealed major differences within segments surrounding the entrance to the retinoid-binding site. These included ␣-helix II and hairpin turns between ␤-strands ␤C-␤D and ␤E-␤F as well as several side chains, such as Phe-57, Tyr-60, and Ile-77, that change their orientations to accommodate the ligand. Additionally, we mapped hydrogen bond networks inside the retinoid-binding cavity and demonstrated their significance for the ligand affinity. Analyses of the crystallographic B-factors indicated several regions with higher backbone mobility in the apoprotein that became more rigid upon retinoid binding. This conformational flexibility of human apo-CRBP1 facilitates interaction with the ligands, whereas the more rigid holoprotein structure protects the labile retinoid moiety during vitamin A transport. These findings suggest a mechanism of induced fit upon ligand binding by mammalian cellular retinol-binding proteins.Effective distribution of vitamin A (all-trans-retinol) and its derivatives (called "retinoids") throughout the body and cellular compartments determines their essential functions in embryonic development, growth, immunology, reproduction, and vision (1-4). However, because of their lipophilic nature, free retinoids exist only at extremely low concentrations in plasma or cytosol, making diffusion kinetics between sites of action inefficient. This solubility limitation is overcome by specialized retinoid-binding proteins that regulate retinoid metabolism and physiological functions (5). Thus, an appreciation of the molecular basis for ligand uptake and targeted release by retinoid-binding proteins is critical for understanding retinoid homeostasis, yet current knowledge of this process is very limited.Three classes of retinoid-binding proteins named for their selectivity (i.e. cellular retinol-binding protein (CRBP), 3 cellular retinoic acid-binding protein, and cis-retinoid-specific cellular retinal-binding proteins) carry vitamin A and its metabolites within cells (5-7). All representatives of CRBPs and cellular retinoic acid-binding proteins are members of intracellular lipid-binding proteins (8), whereas cellular retinal-binding protein belongs to the Sec14 protein family (9). Four CRBPs (CRBP1, -2, -3, and -4) are encoded in the human genome (10, 11). Among them, CRBP1 is the most widely expressed in numerous tissues, with the highest abundance in the liver, kidney, lung, and retinal pigment epithelium cells of the eye (12)(13)(14)...

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Section: Calculations Of Average Crystallographic B-factors and Distrmentioning

confidence: 99%

Ligand Binding Induces Conformational Changes in Human Cellular Retinol-binding Protein 1 (CRBP1) Revealed by Atomic Resolution Crystal Structures

Silvaroli¹,

Arne²,

Chełstowska

et al. 2016

Journal of Biological Chemistry

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“…After extending the resolution to the limit of 1.1 Å and including several additional water molecules, R/R free values were 0.178/0.199, respectively, for F o Ͼ 4(F o ). For further improvement of the model, tightly restrained anisotropic displacement parameters were introduced and refined as recommended (26,27). This reduced both R and R free values by ϳ3%.…”

Section: Methodsmentioning

confidence: 99%

Structure of Plasmodium falciparum Triose-phosphate Isomerase-2-Phosphoglycerate Complex at 1.1-Å Resolution

Parthasarathy

Kandiah

Balaram

et al. 2003

Journal of Biological Chemistry

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Triose-phosphate isomerase, a key enzyme of the glycolytic pathway, catalyzes the isomerization of dihydroxy acetone phosphate and glyceraldehyde 3-phosphate. In this communication we report the crystal structure of Plasmodium falciparum triose-phosphate isomerase complexed to the inhibitor 2-phosphoglycerate at 1.1-Å resolution. The crystallographic asymmetric unit contains a dimeric molecule. The inhibitor bound to one of the subunits in which the flexible catalytic loop 6 is in the open conformation has been cleaved into two fragments presumably due to radiation damage. The cleavage products have been tentatively identified as 2-oxoglycerate and meta-phosphate. The intact 2-phosphoglycerate bound to the active site of the other subunit has been observed in two different orientations. The active site loop in this subunit is in both open and "closed" conformations, although the open form is predominant. Concomitant with the loop closure, Phe-96, Leu-167, and residues 208 -211 (YGGS) are also observed in dual conformations in the B-subunit. Detailed comparison of the active-site geometry in the present case to the Saccharomyces cerevisiae triose-phosphate isomerase-dihydroxy acetone phosphate and Leishmania mexicana triose-phosphate isomerase-phosphoglycolate complexes, which have also been determined at atomic resolution, shows that certain interactions are common to the three structures, although 2-phosphoglycerate is neither a substrate nor a transition state analogue. Triose-phosphate isomerase (TIM)1 is a ubiquitous glycolytic enzyme that catalyzes the isomerization of dihydroxy acetone phosphate (DHAP) and glyceraldehyde 3-phosphate through the intermediate formation of cis-enediol(ate(s)). Commenting on the catalytic efficiency of TIM, Knowles (1) states "This enzyme (TIM) appears to have arrived at the end of its evolutionary development as a catalyst." It has been argued that the evolutionary pressure for TIM to be a perfect catalyst has been intense, since for "flight or fight" there is an instant requirement for muscle ATP. The catalytic reaction of TIM is chemically simple and involves intermolecular protonation and deprotonation between the enzyme and substrate. The enzyme achieves the proton transfers with the help of certain elements as catalytic tools, a 10-residue loop that closes over the active site and stabilizes the reaction intermediate and a catalytic base and an acid to perform the enolization steps (1). It is believed that catalysis is a result of stronger binding of the enzyme to its transition state than to the initial enzyme-substrate complex (2). Although various schemes for this reaction have been proposed (for a review of the schemes, see Cui and Karplus (3)), the most frequently discussed mechanism is the one that involves Glu-165 as the catalytic base in the first proton transfer and His-95 as the catalytic acid for the rest of the reaction (3) (Fig. 1a). Despite numerous experimental (4 -9) and theoretical studies (10, 11), the precise mechanism of the multi-step reaction cataly...

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“…27 The value is greater than 1 when U and V are more similar to each other than to the ADP matrix of an isotropic atom. …”

Section: Activities and Stabilities Of Ctx-m Mutantsmentioning

confidence: 99%

“…The anisotropic movements of the backbone atoms have higher correlation values, quantified by the normalized correlation coefficient, S uij (U,V), as defined in PARVATI and Raster3D. 27,28 An S uij value greater than 1 indicates the anisotropic temperature factors of two atoms are more similar to each other than to an isotropic atom. For CTX-M-27, the mean S uij Figure 5).…”

Section: Active Sitementioning

confidence: 99%

Atomic Resolution Structures of CTX-M β-Lactamases: Extended Spectrum Activities from Increased Mobility and Decreased Stability

Chen

Delmas

Sirot

et al. 2005

Journal of Molecular Biology

136

190

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Comparing anisotropic displacement parameters in protein structures

Cited by 56 publications

References 11 publications

Ligand Binding Induces Conformational Changes in Human Cellular Retinol-binding Protein 1 (CRBP1) Revealed by Atomic Resolution Crystal Structures

Ligand Binding Induces Conformational Changes in Human Cellular Retinol-binding Protein 1 (CRBP1) Revealed by Atomic Resolution Crystal Structures

Structure of Plasmodium falciparum Triose-phosphate Isomerase-2-Phosphoglycerate Complex at 1.1-Å Resolution

Atomic Resolution Structures of CTX-M β-Lactamases: Extended Spectrum Activities from Increased Mobility and Decreased Stability

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