Effect of Nonbilayer Lipids on Membrane Binding and Insertion of the Catalytic Domain of Leader Peptidase†

Biochemistry ◽  
2001 ◽  
Vol 40 (32) ◽  
pp. 9677-9684 ◽  
Author(s):  
Els van den Brink-van der Laan ◽  
Ross E. Dalbey ◽  
Rudy A. Demel ◽  
J. Antoinette Killian ◽  
Ben de Kruijff
Keyword(s):  
Catalytic Domain ◽  
Membrane Binding ◽  
Nonbilayer Lipids ◽  
Leader Peptidase

scholarly journals Membrane interactions with membrane type 1 matrix metalloproteinase

2018 ◽  
Author(s):  
◽  
Tara Marcink
Keyword(s):  
Cell Surface ◽  
Matrix Metalloproteinase ◽  
Catalytic Domain ◽  
Membrane Surface ◽  
Membrane Binding ◽  
Tumor Cell Migration ◽  
Peripheral Protein ◽  
Membrane Type ◽  
Dynamics Simulations

Membrane type 1 matrix metalloproteinase (MT1-MMP) is essential to a myriad of extracellular activities including tumor cell migration and angiogenesis. At the cell surface, MT1-MMP is a major factor in the proteolysis of receptors, growth factors, and collagen. MT1-MMP extracellular domains bind the cell surface which can be influential in bringing these complexes together. This study uses new techniques to uncover the interactions between MT1-MMP and the cell surface. Described here is the development of techniques in protein and lipid preparations, NMR data acquisition, and structure determination by molecular dynamics simulations. Through these methods, the HPX domain was shown to bind nanodiscs by opposing tips of blade II and blade IV. The protruding part of these tips contain an EPGYPK sequence that are seen dipping into the membrane surface making contact with the lipid head groups. Blade IV membrane binding allows collagen to bind unhindered. Both blade II and blade IV membrane binding structures are shown to be favorable for homodimerization without disruption of the collagen binding site. The catalytic domain is shown to at least transiently bind membranes. This study then hypothesizes and discusses how these interactions impact both future peripheral protein membrane interaction studies and uncover similarities between the MMP family.

scholarly journals Disease-linked mutations in the phosphatidylcholine regulatory enzyme CCTα impair enzymatic activity and fold stability

2018 ◽  
Vol 294 (5) ◽  
pp. 1490-1501 ◽  
Author(s):  
Rosemary B. Cornell ◽  
Svetla G. Taneva ◽  
Melissa K. Dennis ◽  
Ronnie Tse ◽  
Randeep K. Dhillon ◽  
...  
Keyword(s):  
Catalytic Domain ◽  
Cultured Cells ◽  
Membrane Binding ◽  
Retinal Dystrophy ◽  
Lipid Vesicles ◽  
Single Amino Acid ◽  
Stringent Requirement ◽  
Catalytic Core ◽  
The Impact

CTP:phosphocholine cytidylyltransferase (CCT) is the key regulatory enzyme in phosphatidylcholine (PC) synthesis and is activated by binding to PC-deficient membranes. Mutations in the gene encoding CCTα (PCYT1A) cause three distinct pathologies in humans: lipodystrophy, spondylometaphyseal dysplasia with cone-rod dystrophy (SMD-CRD), and isolated retinal dystrophy. Previous analyses showed that for some disease-linked PCYT1A variants steady state levels of CCTα and PC synthesis were reduced in patient fibroblasts, but other variants impaired PC synthesis with little effect on CCT levels. To explore the impact on CCT stability and function we expressed WT and mutant CCTs in COS-1 cells, which have very low endogenous CCT. Over-expression of two missense variants in the catalytic domain (V142M and P150A) generated aggregated enzymes that could not be refolded after solubilization by denaturation. Other mutations in the catalytic core that generated CCTs with reduced solubility could be purified. Five variants destabilized the catalytic domain-fold as assessed by lower transition temperatures for unfolding, and three of these manifested defects in substrate Km values. A mutation (R223S) in a signal-transducing linker between the catalytic and membrane-binding domains also impaired enzyme kinetics. E280del, a single amino acid deletion in the autoinhibitory helix increased the constitutive (lipid-independent) enzyme activity ∼4-fold. This helix also participates in membrane binding, and surprisingly E280del enhanced the enzyme's response to anionic lipid vesicles ∼4-fold. These in vitro analyses on purified mutant CCTs will complement future measurements of their impact on PC synthesis in cultured cells and in tissues with a stringent requirement for CCTα.

scholarly journals The Biological Function Prediction of The 10-gingerol Compound of Ginger in Inhibiting Cyclooxygenase-2 Activity

2020 ◽  
Vol 9 (3) ◽  
pp. 222-232
Author(s):  
Gabriella Chandrakirana Krisnamurti ◽  
◽  
Fatchiyah Fatchiyah ◽  
◽  
◽  
...  
Keyword(s):  
Catalytic Domain ◽  
Specific Binding ◽  
Membrane Binding ◽  
Binding Domain ◽  
Cyclooxygenase 2 ◽  
Cyclooxygenase 1 ◽  
Mechanism Of Inhibition ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Anti-inflammatory agents inhibit prostaglandin synthesis by blocking cyclooxygenases (COXs). The compounds extracted from ginger, 10-gingerol and 10-shogaol can inhibit inflammation but the mechanism of inhibition remains unclear. Here we used molecular docking to predict the molecular interactions between COXs and the three inhibitors, acetaminophen (CID1983), 10-gingerol (CID168115) and 10-shogaol (CID6442612). By using that acetaminophen as a gold standard, the results demonstrated that acetaminophen, 10-gingerol, and 10-shogaol could bind catalytic domain and membrane binding domain of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). The 10-shogaol did not show significantly different binding energy to bind to COX-1 and COX-2. The 10-gingerol posed a stronger and more specific binding to the membrane-binding domain of COX-2 than acetaminophen and 10-shogaol. The specific binding of the 10-gingerol to COX-2 could prevent the binding of the natural substrate, arachidonic acid. The results provide useful information to improving activities of anti-inflammatory.

Further insights into the structure of the alternative oxidase: from plants to parasites

2008 ◽  
Vol 36 (5) ◽  
pp. 1022-1026 ◽  
Author(s):  
Anthony L. Moore ◽  
Mary S. Albury
Keyword(s):  
Binding Site ◽  
Alternative Oxidase ◽  
Catalytic Domain ◽  
Membrane Binding ◽  
Experimental Studies ◽  
Catalytic Site ◽  
Current Understanding ◽  
Hydrophobic Pocket ◽  
Complete Reduction ◽  
Plant Kingdom

The AOX (alternative oxidase) is a non-protonmotive ubiquinol–oxygen oxidoreductase that couples the oxidation of ubiquinol with the complete reduction of water. Although it has long been recognized that it is ubiquitous among the plant kingdom, it has only recently become apparent that it is also widely found in other organisms including some human parasites. In this paper, we review experimental studies that have contributed to our current understanding of its structure, with particular reference to the catalytic site. Furthermore, we propose a model for the ubiquinol-binding site which identifies a hydrophobic pocket, between helices II and III, leading from a proposed membrane-binding domain to the catalytic domain.

scholarly journals Phosphatidylethanolamine mediates insertion of the catalytic domain of leader peptidase in membranes

FEBS Letters ◽  
1998 ◽  
Vol 431 (1) ◽  
pp. 75-79 ◽  
Author(s):  
Wim van Klompenburg ◽  
Mark Paetzel ◽  
Joris M. de Jong ◽  
Ross E. Dalbey ◽  
Rudy A. Demel ◽  
...  
Keyword(s):  
Catalytic Domain ◽  
Leader Peptidase

Mechanism for Activation of the EGF Receptor Catalytic Domain by the Juxtamembrane Segment

2009 ◽  
Vol 138 (3) ◽  
pp. 604-604
Author(s):  
Natalia Jura ◽  
Nicholas F. Endres ◽  
Kate Engel ◽  
Sebastian Deindl ◽  
Rahul Das ◽  
...  
Keyword(s):  
Egf Receptor ◽  
Catalytic Domain

Mechanism for Activation of the EGF Receptor Catalytic Domain by the Juxtamembrane Segment

2009 ◽  
Vol 138 (33) ◽  
pp. 604-604
Author(s):  
Natalia Jura ◽  
Nicholas F. Endres ◽  
Kate Engel ◽  
Sebastian Deindl ◽  
Rahul Das ◽  
...  
Keyword(s):  
Egf Receptor ◽  
Catalytic Domain

Author response for "Hypertonic saccharide solution delays pyroptosis in murine macrophages regardless of the membrane binding of gasdermin D N‐terminal"

2019 ◽  
Author(s):  
Jiashuo Zheng ◽  
Dingyu Wang ◽  
Qianyue Chen ◽  
Qiyao Liu ◽  
Zhaoyu Lin ◽  
...  
Keyword(s):  
Membrane Binding ◽  
Author Response ◽  
Murine Macrophages

Author response for "Hypertonic saccharide solution delays pyroptosis in murine macrophages regardless of the membrane binding of gasdermin D N‐terminal"

2019 ◽  
Author(s):  
Jiashuo Zheng ◽  
Dingyu Wang ◽  
Qianyue Chen ◽  
Qiyao Liu ◽  
Zhaoyu Lin ◽  
...  
Keyword(s):  
Membrane Binding ◽  
Author Response ◽  
Murine Macrophages
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