scholarly journals Structural Basis for Allosteric Regulation of GPCRs by Sodium Ions

Science ◽  
2012 ◽  
Vol 337 (6091) ◽  
pp. 232-236 ◽  
Author(s):  
W. Liu ◽  
E. Chun ◽  
A. A. Thompson ◽  
P. Chubukov ◽  
F. Xu ◽  
...  
Keyword(s):  
Allosteric Regulation ◽  
Structural Basis ◽  
Sodium Ions

Structural basis for the allosteric regulation of the SbtA bicarbonate transporter by the PII-like protein, SbtB, from Cyanobium sp. PCC7001

2019 ◽  
Author(s):  
Joe A. Kaczmarski ◽  
Nan-Sook Hong ◽  
Bratati Mukherjee ◽  
Laura T. Wey ◽  
Loraine Rourke ◽  
...  
Keyword(s):  
Metal Ion ◽  
Transcriptional Control ◽  
Allosteric Regulation ◽  
Inhibitory Effect ◽  
Photosynthetic Performance ◽  
Regulatory Proteins ◽  
Structural Basis ◽  
Titration Calorimetry ◽  
X Ray ◽  
Bicarbonate Transporter

ABSTRACTCyanobacteria have evolved a suite of enzymes and inorganic carbon (Ci) transporters that improve photosynthetic performance by increasing the localized concentration of CO2 around the primary CO2-fixating enzyme, Rubisco. This CO2-concentrating mechanism (CCM) is highly regulated, responds to illumination/darkness cycles and allows cyanobacteria to thrive under limiting Ci conditions. While the transcriptional control of CCM activity is well understood, less is known about how regulatory proteins might allosterically regulate Ci transporters in response to changing conditions. Cyanobacterial sodium-dependent bicarbonate transporters (SbtAs) are inhibited by PII-like regulatory proteins (SbtBs), with the inhibitory effect being modulated by adenylnucleotides. Here, we used isothermal titration calorimetry to show that SbtB from Cyanobium sp. PCC7001 (SbtB7001) binds AMP, ADP, cAMP and ATP with micromolar-range affinities. X-ray crystal structures of apo- and nucleotide-bound SbtB7001 revealed that while AMP, ADP and cAMP have little effect on the SbtB7001 structure, binding of ATP stabilizes the otherwise flexible T-loop and that the flexible C-terminal C-loop adopts several distinct conformations. We also show that ATP binding affinity is increased ten-fold in the presence of Ca2+ and we present an X-ray crystal structure of Ca2+ATP:SbtB7001 that shows how this metal ion facilitates additional stabilizing interactions with the apex of the T-loop. We propose that the Ca2+ATP-induced conformational change observed in SbtB7001 is important for allosteric regulation of SbtA activity by SbtB and is consistent with changing adenylnucleotide levels in illumination/darkness cycles.GRAPHICAL ABSTRACT

scholarly journals Structural Basis for Allosteric Regulation in the Major Antenna Trimer of Photosystem II

2019 ◽  
Vol 123 (45) ◽  
pp. 9609-9615 ◽  
Author(s):  
Vangelis Daskalakis ◽  
Sayan Maity ◽  
Cameron Lewis Hart ◽  
Taxiarchis Stergiannakos ◽  
Christopher D. P. Duffy ◽  
...  
Keyword(s):  
Photosystem Ii ◽  
Allosteric Regulation ◽  
Structural Basis

Structure and allosteric regulation of eukaryotic 6-phosphofructokinases

2013 ◽  
Vol 394 (8) ◽  
pp. 977-993 ◽  
Author(s):  
Torsten Schöneberg ◽  
Marco Kloos ◽  
Antje Brüser ◽  
Jürgen Kirchberger ◽  
Norbert Sträter
Keyword(s):  
Crystal Structures ◽  
Structural Information ◽  
Current Knowledge ◽  
Allosteric Regulation ◽  
Site Directed Mutagenesis ◽  
Structural Basis ◽  
Directed Mutagenesis ◽  
Special Focus ◽  
Molecular Architecture ◽  
Key Enzyme

Abstract Although the crystal structures of prokaryotic 6-phosphofructokinase, a key enzyme of glycolysis, have been available for almost 25 years now, structural information about the more complex and highly regulated eukaryotic enzymes is still lacking until now. This review provides an overview of the current knowledge of eukaryotic 6-phosphofructokinase based on recent crystal structures, kinetic analyses and site-directed mutagenesis data with special focus on the molecular architecture and the structural basis of allosteric regulation.

scholarly journals Inter-Enzyme Allosteric Regulation of Chorismate Mutase inCorynebacterium glutamicum: Structural Basis of Feedback Activation by Trp

Biochemistry ◽  
2017 ◽  
Vol 57 (5) ◽  
pp. 557-573 ◽  
Author(s):  
Daniel Burschowsky ◽  
Helen V. Thorbjørnsrud ◽  
Joel B. Heim ◽  
Ju̅ratė Fahrig-Kamarauskaitė ◽  
Kathrin Würth-Roderer ◽  
...  
Keyword(s):  
Allosteric Regulation ◽  
Chorismate Mutase ◽  
Structural Basis ◽  
Feedback Activation

scholarly journals Structural basis for allosteric regulation of pyruvate kinase M2 by phosphorylation and acetylation

2020 ◽  
Vol 295 (51) ◽  
pp. 17425-17440
Author(s):  
Suparno Nandi ◽  
Mortezaali Razzaghi ◽  
Dhiraj Srivastava ◽  
Mishtu Dey
Keyword(s):  
Cancer Cells ◽  
Pyruvate Kinase ◽  
Allosteric Regulation ◽  
Glycolytic Enzyme ◽  
Structural Basis ◽  
Regulation Mechanism ◽  
Oligomeric State ◽  
Structural Reorganization ◽  
The Impact ◽  
Insight Into

Pyruvate kinase muscle isoform 2 (PKM2) is a key glycolytic enzyme and transcriptional coactivator and is critical for tumor metabolism. In cancer cells, native tetrameric PKM2 is phosphorylated or acetylated, which initiates a switch to a dimeric/monomeric form that translocates into the nucleus, causing oncogene transcription. However, it is not known how these post-translational modifications (PTMs) disrupt the oligomeric state of PKM2. We explored this question via crystallographic and biophysical analyses of PKM2 mutants containing residues that mimic phosphorylation and acetylation. We find that the PTMs elicit major structural reorganization of the fructose 1,6-bisphosphate (FBP), an allosteric activator, binding site, impacting the interaction with FBP and causing a disruption in oligomerization. To gain insight into how these modifications might cause unique outcomes in cancer cells, we examined the impact of increasing the intracellular pH (pHi) from ∼7.1 (in normal cells) to ∼7.5 (in cancer cells). Biochemical studies of WT PKM2 (wtPKM2) and the two mimetic variants demonstrated that the activity decreases as the pH is increased from 7.0 to 8.0, and wtPKM2 is optimally active and amenable to FBP-mediated allosteric regulation at pHi 7.5. However, the PTM mimetics exist as a mixture of tetramer and dimer, indicating that physiologically dimeric fraction is important and might be necessary for the modified PKM2 to translocate into the nucleus. Thus, our findings provide insight into how PTMs and pH regulate PKM2 and offer a broader understanding of its intricate allosteric regulation mechanism by phosphorylation or acetylation.

Molecular architecture and structural basis of allosteric regulation of eukaryotic phosphofructokinases

2010 ◽  
Vol 25 (1) ◽  
pp. 89-98 ◽  
Author(s):  
Norbert Strater ◽  
Sascha Marek ◽  
E. Bartholomeus Kuettner ◽  
Marco Kloos ◽  
Antje Keim ◽  
...  
Keyword(s):  
Allosteric Regulation ◽  
Structural Basis ◽  
Molecular Architecture
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