Crystallographic analysis of the interactions of Drosophila melanogaster Golgi α-mannosidase II with the naturally occurring glycomimetic salacinol and its analogues

Kuntz, D.A.; Ghavami, Ahmad; Johnston, Blair D.; Pinto, B. Mario; Rose, David R.

doi:10.1016/j.tetasy.2004.11.057

Cited by 61 publications

(55 citation statements)

References 23 publications

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“…[13] Determination of the IC 50 values (concentrations of inhibitor at which 50 % of activity remains) was carried out with pNPmannose (4 mm) and enzyme (40 nm) as described previously. [22] The K i values for the tight binding inhibitors (swainsonine and 2-4) were assessed in microtiter plates with dGMII (0.5 nm) in a buffer containing MES (40 mm, pH 5.75), bovine serum albumin (50 mg mL À1 ), zinc (10 mm), Triton X100 (0.1 %), phosphate (1 mm), NaCl (10 mm), and DMSO (10 %). Final reaction volume was 80 mL and the reaction was carried out at 258C.…”

Section: Methodsmentioning

confidence: 99%

Structural Investigation of the Binding of 5‐Substituted Swainsonine Analogues to Golgi α‐Mannosidase II

et al. 2010

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Golgi alpha-mannosidase II (GMII) is a key enzyme in the N-glycosylation pathway and is a potential target for cancer chemotherapy. The natural product swainsonine is a potent inhibitor of GMII. In this paper we characterize the binding of 5alpha-substituted swainsonine analogues to the soluble catalytic domain of Drosophila GMII by X-ray crystallography. These inhibitors enjoy an advantage over previously reported GMII inhibitors in that they did not significantly decrease the inhibitory potential of the swainsonine head-group. The phenyl groups of these analogues occupy a portion of the binding site not previously seen to be populated with either substrate analogues or other inhibitors and they form novel hydrophobic interactions. They displace a well-organized water cluster, but the presence of a C(10) carbonyl allows the reestablishment of important hydrogen bonds. Already approximately tenfold more active against the Golgi enzyme than the lysosomal enzyme, these inhibitors offer the potential of being extended into the N-acetylglucosamine binding site of GMII for the creation of even more potent and selective GMII inhibitors.

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Section: Methodsmentioning

confidence: 99%

Structural Investigation of the Binding of 5‐Substituted Swainsonine Analogues to Golgi α‐Mannosidase II

et al. 2010

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“…31,32 The tested compounds 5, 14, 15, 22, 26, 27, 30, 35 and 36 were prepared as stock solutions in DMSO (100 mM) and data were obtained in triplicate over a concentration range of 1-5 mM. Jack bean α-mannosidase (5μL) was pre-incubated for 5 min at 20°C with the inhibitor under evaluation.…”

Section: Biochemistrymentioning

confidence: 99%

Synthesis of modified D-mannose core derivatives and their impact on GH38 α-mannosidases

Poláková

Horák

Šesták

et al. 2016

Carbohydrate Research

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“…Map quality was judged initially by visual inspection and quantified by calculating the correlation coefficient with the final refined 2mFo À DF c map using PHENIX (Adams et al, 2011). Of the density-modification programs tested, Parrot (Zhang et al, 1997;Cowtan, 2010) delivered the best maps, which could be further improved slightly by using PDB entry 4zgf (Joint Center for Structural Genomics, unpublished work) as a reference data set for histogram matching rather than the default PDB entry 1tqw (Kuntz et al, 2005).…”

Section: Sad Phasing and Density Modificationmentioning

confidence: 99%

Atomic resolution experimental phase information reveals extensive disorder and bound 2-methyl-2,4-pentanediol in Ca²⁺-calmodulin

Lin

Bedem

Brunger

et al. 2016

Acta Cryst Sect D Struct Biol

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Calmodulin (CaM) is the primary calcium signaling protein in eukaryotes and has been extensively studied using various biophysical techniques. Prior crystal structures have noted the presence of ambiguous electron density in both hydrophobic binding pockets of Ca2+-CaM, but no assignment of these features has been made. In addition, Ca2+-CaM samples many conformational substates in the crystal and accurately modeling the full range of this functionally important disorder is challenging. In order to characterize these features in a minimally biased manner, a 1.0 Å resolution single-wavelength anomalous diffraction data set was measured for selenomethionine-substituted Ca2+-CaM. Density-modified electron-density maps enabled the accurate assignment of Ca2+-CaM main-chain and side-chain disorder. These experimental maps also substantiate complex disorder models that were automatically built using low-contour features of model-phased electron density. Furthermore, experimental electron-density maps reveal that 2-methyl-2,4-pentanediol (MPD) is present in the C-terminal domain, mediates a lattice contact between N-terminal domains and may occupy the N-terminal binding pocket. The majority of the crystal structures of target-free Ca2+-CaM have been derived from crystals grown using MPD as a precipitant, and thus MPD is likely to be bound in functionally critical regions of Ca2+-CaM in most of these structures. The adventitious binding of MPD helps to explain differences between the Ca2+-CaM crystal and solution structures and is likely to favor more open conformations of the EF-hands in the crystal.

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Crystallographic analysis of the interactions of Drosophila melanogaster Golgi α-mannosidase II with the naturally occurring glycomimetic salacinol and its analogues

Cited by 61 publications

References 23 publications

Structural Investigation of the Binding of 5‐Substituted Swainsonine Analogues to Golgi α‐Mannosidase II

Structural Investigation of the Binding of 5‐Substituted Swainsonine Analogues to Golgi α‐Mannosidase II

Synthesis of modified D-mannose core derivatives and their impact on GH38 α-mannosidases

Atomic resolution experimental phase information reveals extensive disorder and bound 2-methyl-2,4-pentanediol in Ca²⁺-calmodulin

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Crystallographic analysis of the interactions of Drosophila melanogaster Golgi α-mannosidase II with the naturally occurring glycomimetic salacinol and its analogues

Cited by 61 publications

References 23 publications

Structural Investigation of the Binding of 5‐Substituted Swainsonine Analogues to Golgi α‐Mannosidase II

Structural Investigation of the Binding of 5‐Substituted Swainsonine Analogues to Golgi α‐Mannosidase II

Synthesis of modified D-mannose core derivatives and their impact on GH38 α-mannosidases

Atomic resolution experimental phase information reveals extensive disorder and bound 2-methyl-2,4-pentanediol in Ca2+-calmodulin

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Atomic resolution experimental phase information reveals extensive disorder and bound 2-methyl-2,4-pentanediol in Ca²⁺-calmodulin