Crystal structure of DMGO provides a prototype for a new tetrahydrofolate-binding fold

2005 ◽  
Vol 33 (4) ◽  
pp. 776-779 ◽  
Author(s):  
N.S. Scrutton ◽  
D. Leys
Keyword(s):  
Crystal Structure ◽  
Binding Site ◽  
Crystal Structures ◽  
Binding Proteins ◽  
Arthrobacter Globiformis ◽  
Fold Family ◽  
Folate Binding Proteins

The crystal structure of DMGO (dimethylglycine oxidase) from Arthrobacter globiformis in complex with folate compounds has revealed a novel THF (tetrahydrofolate)-binding fold [Leys, Basran and Scrutton (2003) EMBO J. 22, 4038–4048]. This fold is widespread among folate-binding proteins. The crystal structures of aminomethyltransferase (T-protein), YgfZ and TrmE all reveal similar THF-binding folds despite little similarity in sequence or function. The THF-binding site is highly specific for reduced folate compounds and most members of this fold family enhance the nucleophilic character of the THF N10 position.

scholarly journals Calixarene-mediated assembly of a small antifungal protein

IUCrJ ◽  
2019 ◽  
Vol 6 (2) ◽  
pp. 238-247 ◽  
Author(s):  
Jimi M. Alex ◽  
Martin L. Rennie ◽  
Sylvain Engilberge ◽  
Gábor Lehoczki ◽  
Hajdu Dorottya ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Antifungal Activity ◽  
High Resolution ◽  
Complex Formation ◽  
Binding Site ◽  
Crystal Structures ◽  
Protein Assembly ◽  
Bidentate Ligand ◽  
Antifungal Protein ◽  
Protein Recognition

Synthetic macrocycles such as calixarenes and cucurbiturils are increasingly applied as mediators of protein assembly and crystallization. The macrocycle can facilitate assembly by providing a surface on which two or more proteins bind simultaneously. This work explores the capacity of the sulfonato-calix[n]arene (sclx n ) series to effect crystallization of PAF, a small, cationic antifungal protein. Co-crystallization with sclx4, sclx6 or sclx8 led to high-resolution crystal structures. In the absence of sclx n , diffraction-quality crystals of PAF were not obtained. Interestingly, all three sclx n were bound to a similar patch on PAF. The largest and most flexible variant, sclx8, yielded a dimer of PAF. Complex formation was evident in solution via NMR and ITC experiments, showing more pronounced effects with increasing macrocycle size. In agreement with the crystal structure, the ITC data suggested that sclx8 acts as a bidentate ligand. The contributions of calixarene size/conformation to protein recognition and assembly are discussed. Finally, it is suggested that the conserved binding site for anionic calixarenes implicates this region of PAF in membrane binding, which is a prerequisite for antifungal activity.

Helicase mechanisms and the coupling of helicases within macromolecular machines Part I: Structures and properties of isolated helicases

2002 ◽  
Vol 35 (4) ◽  
pp. 431-478 ◽  
Author(s):  
Emmanuelle Delagoutte ◽  
Peter H. von Hippel
Keyword(s):  
Crystal Structure ◽  
Nucleic Acid ◽  
Nucleic Acids ◽  
Binding Site ◽  
Crystal Structures ◽  
Base Pair ◽  
Biochemical Properties ◽  
Functional Coupling ◽  
Hexameric Helicases ◽  
Base Pair Opening

1. Mechanisms of nucleic acid (NA) unwinding by helicases 4322. Helicases may take advantage of ‘breathing’ fluctuations in dsNAs 4342.1 Stability and dynamics of dsNAs 4342.2 dsNAs ‘breathe’ in isolation 4352.3 Thermodynamics of terminal base pairs of dsNA 4382.4 Thermal fluctuations may be responsible for sequential base-pair opening at replication forks 4392.5 Helicases may capture single base-pair opening events sequentially 4403. Biochemical properties of helicases 4433.1 Binding of NAs 4433.2 Binding and hydrolysis of NTP 4453.3 Coordination between NA binding and NTP binding and hydrolysis activities 4464. Helicase structures and mechanistic consequences 4474.1 Amino-acid sequence analysis reveals conserved motifs that constitute the NTP-binding pocket and a portion of the NA-binding site 4474.2 Organization of hepatitis virus C NS3 RNA helicase 4494.2.1 Biochemical properties of HCV NS3 4494.2.2 Crystal structures of HCV NS3 helicase 4504.2.2.1 The apoprotein 4504.2.2.2 The protein–dU8 complex 4504.2.3 A possible unwinding mechanism 4524.2.4 What is the functional oligomeric state of HCV NS3? 4524.3 Organization of the PcrA helicase 4534.3.1 The apoenzyme and ADP–PcrA complex 4544.3.2 The protein–DNA–sulfate complex 4564.3.3 The PcrA–DNA–ADPNP complex 4564.3.4 A closer look at the NTP-binding site in the crystal structure of PcrA–ADPNP–DNA 4574.3.5 Communication between domains A and B 4574.3.6 How might ssDNA stimulate the ATPase activity of PcrA? 4574.3.7 A possible helicase translocation mechanism 4584.3.8 A possible unwinding mechanism 4584.4 Organization of the Rep helicase 4594.4.1 Biochemical properties 4594.4.2 Crystal structure of Rep bound to ssDNA 4624.5 Organization of the RecG helicase 4624.6 Hexameric helicases 4664.6.1 Insights from crystal structures of hexameric helicases 4674.6.2 Possible translocation and unwinding mechanisms 4685. Conclusions 4696. Acknowledgments 4727. References 472Helicases are proteins that harness the chemical free energy of ATP hydrolysis to catalyze the unwinding of double-stranded nucleic acids. These enzymes have been much studied in isolation, and here we review what is known about the mechanisms of the unwinding process. We begin by considering the thermally driven ‘breathing’ of double-stranded nucleic acids by themselves, in order to ask whether helicases might take advantage of some of these breathing modes. We next provide a brief summary of helicase mechanisms that have been elucidated by biochemical, thermodynamic, and kinetic studies, and then review in detail recent structural studies of helicases in isolation, in order to correlate structural findings with biophysical and biochemical results. We conclude that there are certainly common mechanistic themes for helicase function, but that different helicases have devised solutions to the nucleic acid unwinding problem that differ in structural detail. In Part II of this review (to be published in the next issue of this journal) we consider how these mechanisms are further modified to reflect the functional coupling of these proteins into macromolecular machines, and discuss the role of helicases in several central biological processes to illustrate how this coupling actually works in the various processes of gene expression.

scholarly journals Conformational interconversion of MLKL and disengagement from RIPK3 precede cell death by necroptosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sarah E. Garnish ◽  
Yanxiang Meng ◽  
Akiko Koide ◽  
Jarrod J. Sandow ◽  
Eric Denbaum ◽  
...  
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Binding Site ◽  
Crystal Structures ◽  
Conformational Change ◽  
Binding Proteins ◽  
Conformational Transition ◽  
Human Cells ◽  
Conformational Interconversion ◽  
Large Conformational Change

AbstractPhosphorylation of the MLKL pseudokinase by the RIPK3 kinase leads to MLKL oligomerization, translocation to, and permeabilization of, the plasma membrane to induce necroptotic cell death. The precise choreography of MLKL activation remains incompletely understood. Here, we report Monobodies, synthetic binding proteins, that bind the pseudokinase domain of MLKL within human cells and their crystal structures in complex with the human MLKL pseudokinase domain. While Monobody-32 constitutively binds the MLKL hinge region, Monobody-27 binds MLKL via an epitope that overlaps the RIPK3 binding site and is only exposed after phosphorylated MLKL disengages from RIPK3 following necroptotic stimulation. The crystal structures identified two distinct conformations of the MLKL pseudokinase domain, supporting the idea that a conformational transition accompanies MLKL disengagement from RIPK3. These studies provide further evidence that MLKL undergoes a large conformational change upon activation, and identify MLKL disengagement from RIPK3 as a key regulatory step in the necroptosis pathway.

Synthesis and crystal structure of a novel phthalocyanine-calixarene conjugate

2011 ◽  
Vol 15 (07n08) ◽  
pp. 686-690 ◽  
Author(s):  
C. Grazia Bezzu ◽  
Madeleine Helliwell ◽  
Benson M. Kariuki ◽  
Neil B. McKeown
Keyword(s):  
Crystal Structure ◽  
Optical Properties ◽  
Binding Site ◽  
Crystal Structures ◽  
Chemical Species ◽  
Synthesis And Crystal Structure ◽  
Molecular Sensor

We report the synthesis and crystal structure of a novel phthalocyanine-calixarene conjugate (Pc-Calix) derived from a calixarene-based phthalonitrile (Pn-Calix). Crystal structures confirm the retention of the full cone configuration of the calixarene unit, which is thus suitable for the binding of appropriate chemical species. This new conjugate may find application as a molecular sensor in which the calixarene acts as the binding site and the perturbations of the optical properties of the phthalocyanine reports the presence of the binding species.

Effect of solution acidity on the crystallization of polychromates in uranyl-bearing systems: synthesis and crystal structures of Rb2[(UO2)(Cr2O7)(NO3)2] and two new polymorphs of Rb2Cr3O10

2021 ◽  
Vol 236 (1-2) ◽  
pp. 11-21
Author(s):  
Evgeny V. Nazarchuk ◽  
Oleg I. Siidra ◽  
Dmitry O. Charkin ◽  
Stepan N. Kalmykov ◽  
Elena L. Kotova
Keyword(s):  
Crystal Structure ◽  
Aqueous Solutions ◽  
Crystal Structures ◽  
Hydrothermal Treatment ◽  
Ambient Conditions ◽  
Screw Axis ◽  
3D Framework ◽  
Solution Acidity

Abstract Three new rubidium polychromates, Rb2[(UO2)(Cr2O7)(NO3)2] (1), γ-Rb2Cr3O10 (2) and δ-Rb2Cr3O10 (3) were prepared by combination of hydrothermal treatment at 220 °C and evaporation of aqueous solutions under ambient conditions. Compound 1 is monoclinic, P 2 1 / c $P{2}_{1}/c$ , a = 13.6542(19), b = 19.698(3), c = 11.6984(17) Å, β = 114.326(2)°, V = 2867.0(7) Å3, R 1 = 0.040; 2 is hexagonal, P 6 3 / m $P{6}_{3}/m$ , a = 11.991(2), c = 12.828(3) Å, γ = 120°, V = 1597.3(5) Å3, R 1 = 0.031; 3 is monoclinic, P 2 1 / n $P{2}_{1}/n$ , a = 7.446(3), b = 18.194(6), c = 7.848(3) Å, β = 99.953(9)°, V = 1047.3(7) Å3, R 1 = 0.037. In the crystal structure of 1, UO8 bipyramids and NO3 groups share edges to form [(UO2)(NO3)2] species which share common corners with dichromate Cr2O7 groups producing novel type of uranyl dichromate chains [(UO2)(Cr2O7)(NO3)2]2−. In the structures of new Rb2Cr3O10 polymorphs, CrO4 tetrahedra share vertices to form Cr3O10 2− species. The trichromate groups are aligned along the 63 screw axis forming channels running in the ab plane in the structure of 2. The Rb cations reside between the channels and in their centers completing the structure. The trichromate anions are linked by the Rb+ cations into a 3D framework in the structure of 3. Effect of solution acidity on the crystallization of polychromates in uranyl-bearing systems is discussed.

scholarly journals Crystal Chemical Relations in the Shchurovskyite Family: Synthesis and Crystal Structures of K2Cu[Cu3O]2(PO4)4 and K2.35Cu0.825[Cu3O]2(PO4)4

Crystals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 807
Author(s):  
Ilya V. Kornyakov ◽  
Sergey V. Krivovichev
Keyword(s):  
Crystal Structure ◽  
Crystal Structures ◽  
Structural Complexity ◽  
Crystal Chemical ◽  
X Ray Diffraction ◽  
Complexity Measures ◽  
X Ray ◽  
The Family ◽  
Similarities And Differences ◽  
Related Compounds

Single crystals of two novel shchurovskyite-related compounds, K2Cu[Cu3O]2(PO4)4 (1) and K2.35Cu0.825[Cu3O]2(PO4)4 (2), were synthesized by crystallization from gaseous phase and structurally characterized using single-crystal X-ray diffraction analysis. The crystal structures of both compounds are based upon similar Cu-based layers, formed by rods of the [O2Cu6] dimers of oxocentered (OCu4) tetrahedra. The topologies of the layers show both similarities and differences from the shchurovskyite-type layers. The layers are connected in different fashions via additional Cu atoms located in the interlayer, in contrast to shchurovskyite, where the layers are linked by Ca2+ cations. The structures of the shchurovskyite family are characterized using information-based structural complexity measures, which demonstrate that the crystal structure of 1 is the simplest one, whereas that of 2 is the most complex in the family.

scholarly journals Structural insights into targeting of the colchicine binding site by ELR510444 and parbendazole to achieve rational drug design

RSC Advances ◽  
2021 ◽  
Vol 11 (31) ◽  
pp. 18938-18944
Author(s):  
Jia-Hong Lei ◽  
Ling-Ling Ma ◽  
Jing-Hong Xian ◽  
Hai Chen ◽  
Jian-Jian Zhou ◽  
...  
Keyword(s):  
Drug Design ◽  
Binding Site ◽  
Crystal Structures ◽  
Rational Drug Design ◽  
Colchicine Binding Site ◽  
Rational Drug ◽  
Structural Insights

Crystal structures of tubulin complexed with ELR510444 and parbendazole facilitate the design of novel colchicine binding site inhibitors.

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