Ophanin

Key takeaways

Ophanin belongs to science; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Ophanin to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Ophanin from memory before moving on to harder problems.

Reference excerpt

Ophanin is a toxin found in the venom of the King Cobra (Ophiophagus hannah), which lives throughout South East Asia. This toxin belongs to the cysteine-rich secretory protein (CRISP) family. Ophanin weakly blocks the contraction of smooth muscles elicited by high potassium-induced depolarization, suggesting that it inhibits voltage-dependent calcium channels.

Etymology

The toxin was named ophanin after the snake whose venom it is derived from, the King Cobra (Ophiophagus hannah).

Sources Ophanin is produced in the venom glands of the King Cobra (O. Hannah). Although the venom has relatively low toxicity, this is compensated by the high amounts of it injected into the prey for each bite.

Chemistry

Structure Ophanin was successfully isolated from O. Hannah venom by gel filtration and cation-exchange chromatography. Its molecular weight is 25 kDa (from positions 19 – 239), which conforms to the molecular mass predicted from its cDNA sequences.

Homology Ophanin is a cysteine-rich secretory protein and therefore belongs to the CRISP family. These proteins possess 16 strictly conserved cysteines and contain 8 disulfide bonds. Ten of the 16 cysteine residues are clustered at the C-terminal end of the protein. Ophanin belongs to the “long” CRISPs subgroup, which consists of the 9 CRISPs with the longest sequences. Snake venom CRISPs belonging to different subgroups act on different biological targets, contributing in this way to the diversity of damaging effects of snake venoms.

Family The phylogenetic tree constructed from the nucleotide sequences of all known snake venom CRISPs shows that ophanin is more closely related to the Viperidae branch than the Elapidae branch even though O. Hannah belongs to the Elapidae snakes. Ophanin, along with other specific snake toxins like triflin and ablomin, is also a helothermine-related venom protein (Helveprin) which was originally isolated from the skin of the Mexican beaded lizard.

Target Ophanin is a weak blocker of the high potassium-induced contraction of smooth muscles. Snake venom CRISP family proteins inhibit depolarization-induced smooth muscle contraction to different extents. Compared to the normal contraction of smooth muscle, ophanin is able to reduce their force of contractility to 84% ± 1%, which is less than most other CRISPs. The differences between the inhibitory activity of CRISPs may be explained through sequence comparisons that suggest a site that may be critical for inhibition of channel activity. Phe189 and Glu186 are the most likely functional residues: strong blockers of smooth muscle contraction (ablomin, triflin, and latisemin) all have Phe189, and all blockers of smooth muscle contraction except ophanin have Glu186. The significance of this lack of the probable functional residues in ophanin has not yet been addressed. However, it is likely that the picture is more complex and other residues contribute to the inhibitory activity of CRISPs on smooth muscle contraction and some data supports this. For example, pseudecin, while also having Phe189, does not affect depolarization-induced contraction.

Mode of action There is no direct evidence of a particular mode of action of ophanin blocking depolarization-induced contractions of the smooth muscles. However, based on the hypothesis of Yamazaki and colleagues in regards to ablomin, another snake venom toxin from the CRISP family that also blocks depolarization-induced smooth muscle contraction, we can postulate a similar mechanism might be in place for ophanin. Since ablomin only blocks contraction induced by depolarization, but not by caffeine, the effect of ablomin is likely to be caused by inhibition of voltage-gated ion channels. An activation of smooth muscle cells through caffeine activates ryanodine receptors of the sarcoplasmic reticulum, whereas an activation through high levels of extracellular potassium depolarizes the membrane (due to the change of the reversal potential for potassium towards more positive values) and would then activate voltage-gated calcium-ion channels leading to high levels of intracellular calcium ions. The intracellular calcium ion concentration correlates well with contraction force in the rat-tail artery. Thus, contraction following extracellular application of high-potassium solution depends on the influx of the extracellular calcium ions through voltage-gated calcium channels. Therefore, ablomin (and by extension ophanin) most likely targets voltage-gated calcium channels on smooth muscle.

Toxicity The LD50 of the venom in mice is ~1.2 to 3.5 mg/kg via intravenous injection. The LD50 of ophanin is not yet known.

See also Other snake venom proteins in the CRISP family: Piscivorin from the Eastern Cottonmouth Triflin from the Habu snake Ablomin from the Mamushi snake Latisemin from the Erabu snake

References

Worked examples

Example 1 — a first encounter with Ophanin

Start with the simplest possible case. Write down what Ophanin claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In science, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Ophanin before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Ophanin ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Ophanin

In research: Ophanin appears in science research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Ophanin in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Ophanin is common in secondary-school and first-year university syllabi. It links to neighbouring topics Ion channel toxins, Snake toxins, so understanding it makes those chapters shorter.
In everyday life: Look for Ophanin outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study Ophanin in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Ophanin means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Ophanin out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Ophanin in simple terms?

Ophanin is a toxin found in the venom of the King Cobra (Ophiophagus hannah), which lives throughout South East Asia. This toxin belongs to the cysteine-rich secretory protein (CRISP) family.

Why does Ophanin matter?

Because it connects several science ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Ophanin?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Ophanin.