Related Experiment Video

Updated: Jul 30, 2026

Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
09:42

Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes

Published on: January 16, 2016

Dynamic characterization of the water binding loop in the P-type cardiotoxin: implication for the role of the bound

S C Sue1, H C Jarrell, J R Brisson

  • 1Department of Life Sciences, National Tsing Hua University, Hsinchu 30043, Taiwan.

Biochemistry
|October 24, 2001
PubMed

Insights

Bound water in cobra cardiotoxins (CTXs) is crucial for membrane binding and cytotoxicity. This study reveals a dynamic, solvent-accessible water molecule in CTX A3, suggesting its exchange rate regulates lipid binding.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Toxicology

Background:

  • P-type cardiotoxins (CTXs) from cobras are known for their membrane-disrupting and cytotoxic effects.
  • The water-binding loop (loop II) is implicated in CTX membrane interactions and cytotoxicity.

Purpose of the Study:

  • To elucidate the role of bound water in the loop II of CTX A3 from the Taiwan cobra.
  • To understand the structure and dynamics of the water molecule bound to CTX A3.

Main Methods:

  • Comprehensive Nuclear Magnetic Resonance (NMR) analysis, including (1)H NOESY/ROESY, (13)C[1)H]NOE/T(1) relaxation, and (17)O triple-quantum filtered NMR.
  • Structural and dynamic characterization of CTX A3.

Main Results:

  • A single water molecule is tightly hydrogen-bonded to Met26 in CTX A3.
  • This bound water exhibits a long residence time and is located in a dynamic, solvent-accessible loop.
  • Proline residues in the consensus sequence (MxAxPxVPV) are suggested to be important for water loop formation across P-type CTXs.

Conclusions:

  • The bound water molecule in CTX A3's loop II is dynamic and accessible, despite its tight binding.
  • The exchange rate of this bound water may regulate the lipid-binding mode of amphiphilic CTXs at membrane surfaces.

More Related Videos

Site Directed Spin Labeling and EPR Spectroscopic Studies of Pentameric Ligand-Gated Ion Channels11:19

Site Directed Spin Labeling and EPR Spectroscopic Studies of Pentameric Ligand-Gated Ion Channels

Published on: July 4, 2016

Structure-Guided Design and Development of Novel Cyclophilin A Inhibitors and Ganoderiol-F Derivatives: An In-Silico Approach10:01

Structure-Guided Design and Development of Novel Cyclophilin A Inhibitors and Ganoderiol-F Derivatives: An In-Silico Approach

Published on: June 23, 2026

Related Concept Videos

Water: A Bronsted-Lowry Acid and Base02:30

Water: A Bronsted-Lowry Acid and Base

The reaction between a Brønsted-Lowry acid and water is called acid ionization. For example, when hydrogen fluoride dissolves in water and ionizes, protons are transferred from hydrogen fluoride molecules to water molecules, yielding hydronium ions and fluoride ions:
Ligand Binding Sites02:40

Ligand Binding Sites

Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Aquaporins01:25

Aquaporins

Aquaporins or AQPs are a family of integral membrane proteins whose primary function is to transport water, while some called aquaglyceroporins also transport glycerol. In addition, aquaporins have also been suspected to be involved in transporting volatile substances, such as carbon dioxide and ammonia, across membranes. Such AQPs that act as gas channels are often highly expressed in cells involved in the gaseous exchange, such as red blood cells, epithelial cells, and pulmonary capillaries.
Resting Membrane Potential01:24

Resting Membrane Potential

The relative difference in electrical charge, or voltage, between the inside and the outside of a cell membrane, is called the membrane potential. It is generated by differences in permeability of the membrane to various ions and the concentrations of these ions across the membrane.
The Inside of a Neuron is More Negative
The membrane potential of a cell can be measured by inserting a microelectrode into a cell and comparing the charge to a reference electrode in the extracellular fluid. The...
ATP Driven Pumps II: P-type Pumps01:34

ATP Driven Pumps II: P-type Pumps

The P-type pumps are a large family of integral membrane transporter ATPases. They are divided into five major types based on substrate specificity, from I to V.
A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...