Conformational Changes in the α-Subunit Coupled to Binding of the β2-Subunit of Tryptophan Synthase fromEscherichia coli:  Crystal Structure of the Tryptophan Synthase α-Subunit Alone†,‡

Biochemistry ◽  
2005 ◽  
Vol 44 (4) ◽  
pp. 1184-1192 ◽  
Author(s):  
Kazuya Nishio ◽  
Yukio Morimoto ◽  
Manabu Ishizuka ◽  
Kyoko Ogasahara ◽  
Tomitake Tsukihara ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Conformational Changes ◽  
Tryptophan Synthase ◽  
Α Subunit ◽  
Fromescherichia Coli

Conformational Changes in the Tryptophan Synthase from a Hyperthermophile upon α2β2Complex Formation:  Crystal Structure of the Complex†,‡

Biochemistry ◽  
2005 ◽  
Vol 44 (34) ◽  
pp. 11417-11427 ◽  
Author(s):  
Soo Jae Lee ◽  
Kyoko Ogasahara ◽  
Jichun Ma ◽  
Kazuya Nishio ◽  
Masami Ishida ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Conformational Changes ◽  
Tryptophan Synthase

Crystal Structure of Na+, K+-ATPase in the Na+-Bound State

Science ◽  
2013 ◽  
Vol 342 (6154) ◽  
pp. 123-127 ◽  
Author(s):  
Maria Nyblom ◽  
Hanne Poulsen ◽  
Pontus Gourdon ◽  
Linda Reinhard ◽  
Magnus Andersson ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Conformational Changes ◽  
Structural Information ◽  
Bound State ◽  
Electrical Excitability ◽  
Α Subunit ◽  
Γ Subunit ◽  
Extracellular Release ◽  
Unique Site ◽  
Electrophysiological Studies

The Na+, K+–adenosine triphosphatase (ATPase) maintains the electrochemical gradients of Na+ and K+ across the plasma membrane—a prerequisite for electrical excitability and secondary transport. Hitherto, structural information has been limited to K+-bound or ouabain-blocked forms. We present the crystal structure of a Na+-bound Na+, K+-ATPase as determined at 4.3 Å resolution. Compared with the K+-bound form, large conformational changes are observed in the α subunit whereas the β and γ subunit structures are maintained. The locations of the three Na+ sites are indicated with the unique site III at the recently suggested IIIb, as further supported by electrophysiological studies on leak currents. Extracellular release of the third Na+ from IIIb through IIIa, followed by exchange of Na+ for K+ at sites I and II, is suggested.

Improved resolution crystal structure of Acanthamoeba actophorin reveals structural plasticity not induced by microgravity

2021 ◽  
Vol 77 (12) ◽  
Author(s):  
Stephen Quirk ◽  
Raquel L. Lieberman
Keyword(s):  
Crystal Structure ◽  
Conformational Changes ◽  
Actin Filaments ◽  
Space Station ◽  
Acanthamoeba Castellanii ◽  
Test Case ◽  
Molecular Replacement ◽  
International Space ◽  
Microgravity Conditions ◽  
Turn Region

Actophorin, a protein that severs actin filaments isolated from the amoeba Acanthamoeba castellanii, was employed as a test case for crystallization under microgravity. Crystals of purified actophorin were grown under microgravity conditions aboard the International Space Station (ISS) utilizing an interactive crystallization setup between the ISS crew and ground-based experimenters. Crystals grew in conditions similar to those grown on earth. The structure was solved by molecular replacement at a resolution of 1.65 Å. Surprisingly, the structure reveals conformational changes in a remote β-turn region that were previously associated with actophorin phosphorylated at the terminal residue Ser1. Although crystallization under microgravity did not yield a higher resolution than crystals grown under typical laboratory conditions, the conformation of actophorin obtained from solving the structure suggests greater flexibility in the actophorin β-turn than previously appreciated and may be beneficial for the binding of actophorin to actin filaments.

scholarly journals Minimal mechanistic component of proteasome activation and prevention of impairment by pathological oligomers

2021 ◽  
Author(s):  
Janelle Chuah ◽  
Tifffany Thibaudeau ◽  
David Smith
Keyword(s):  
Small Molecules ◽  
Conformational Changes ◽  
Bound State ◽  
Proof Of Concept ◽  
Α Subunit ◽  
Gate Opening ◽  
Allosteric Mechanism ◽  
Dependent Mechanism ◽  
Degradation Of Peptides

Abstract Impairment of proteasomal function has been implicated in neurodegenerative diseases, justifying the need to understand how the proteasome is activated for protein degradation. Here, using biochemical and structural (cryo-EM) strategies in both archaeal and mammalian proteasomes, we further determine the HbYX(-motif)-dependent mechanism of proteasomal activation used by multiple proteasome-activating complexes including the 19S Particle. We identify multiple proteasome α subunit residues involved in HbYX-dependent activation, a point mutation that activates the proteasome by partially mimicking a HbYX-bound state, and conformational changes involved in gate-opening with a 2.0A structure. Through an iterative process of peptide synthesis, we successfully design a HbYX-like dipeptide mimetic as a robust tool to elucidate how the motif autonomously activates the proteasome. The mimetic induces near complete gate-opening at saturating concentration, activating mammalian proteasomal degradation of peptides and proteins. Findings using our peptide mimetic suggest the HbYX-dependent mechanism requires cooperative binding in at least two intersubunit pockets of the α ring. Collectively, the results presented here unambiguously demonstrate the lone role of the HbYX tyrosine in the allosteric mechanism of proteasome activation and offer proof of concept for the robust potential of HbYX-like small molecules to activate the proteasome.

scholarly journals Crystal structure of SARS-CoV-2 main protease in complex with a Chinese herb inhibitor shikonin

2020 ◽  
Author(s):  
Jian Li ◽  
Xuelan Zhou ◽  
Yan Zhang ◽  
Fanglin Zhong ◽  
Cheng Lin ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Conformational Changes ◽  
Drug Targets ◽  
Chinese Herb ◽  
Binding Modes ◽  
High Potency ◽  
Main Protease ◽  
Covalent Inhibitors ◽  
Catalytic Dyad ◽  
Important Drug

AbstractMain protease (Mpro, also known as 3CLpro) has a major role in the replication of coronavirus life cycle and is one of the most important drug targets for anticoronavirus agents. Here we report the crystal structure of main protease of SARS-CoV-2 bound to a previously identified Chinese herb inhibitor shikonin at 2.45 angstrom resolution. Although the structure revealed here shares similar overall structure with other published structures, there are several key differences which highlight potential features that could be exploited. The catalytic dyad His41-Cys145 undergoes dramatic conformational changes, and the structure reveals an unusual arrangement of oxyanion loop stabilized by the substrate. Binding to shikonin and binding of covalent inhibitors show different binding modes, suggesting a diversity in inhibitor binding. As we learn more about different binding modes and their structure-function relationships, it is probable that we can design more effective and specific drugs with high potency that can serve as effect SARS-CoV-2 anti-viral agents.

Crystal structure of the stromelysin catalytic domain at 2.0 Å resolution: inhibitor-induced conformational changes 1 1Edited by R. Huber

1999 ◽  
Vol 293 (3) ◽  
pp. 545-557 ◽  
Author(s):  
Longyin Chen ◽  
Timothy J Rydel ◽  
Fei Gu ◽  
C.Michelle Dunaway ◽  
Stanislaw Pikul ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Conformational Changes ◽  
Catalytic Domain
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