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Lipoyl synthase

Lipoyl synthase is a engineering topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Lipoyl synthase rather than just read about it. In short: Lipoyl synthase is an enzyme that belongs to the radical SAM (S-adenosyl methionine) family. Within the radical SAM superfamily, lipoyl synthase is in a sub-family of enzymes that catalyze sulfur insertion reactions.

Lipoyl synthase — main illustration
Lipoyl synthase — illustration

Key takeaways

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

Reference excerpt

Lipoyl synthase is an enzyme that belongs to the radical SAM (S-adenosyl methionine) family. Within the radical SAM superfamily, lipoyl synthase is in a sub-family of enzymes that catalyze sulfur insertion reactions. The enzymes in this subfamily differ from general radical SAM enzymes, as they contain two 4Fe-4S clusters. From these clusters, the enzymes obtain the sulfur groups that will be transferred onto the corresponding substrates. This particular enzyme participates in the final step of lipoic acid metabolism, transferring two sulfur atoms from its 4Fe-4S cluster onto the protein N6-(octanoyl)lysine through radical generation. This enzyme is usually localized to the mitochondria. Two organisms that have been extensively studied with regards to this enzyme are Escherichia coli and Mycobacterium tuberculosis. It is currently being studied in other organisms including yeast, plants, and humans.

Nomenclature The systematic name of this enzyme class is protein N6-(octanoyl)lysine:sulfur sulfurtransferase. Other names in common use include:

LS LipA lipoate synthase protein 6-N-(octanoyl)lysine:sulfur sulfurtransferase.

Structure The sequence length of M. tuberculosis lipoyl synthase is approximately 331 amino acids. The structure is composed of 11 α-helices and 7 β sheets, with multiple loop structures connecting the other components. The two [4Fe-4S] clusters are located within the structure, appearing in three-dimensional cubic shape. A molecule of DTV ((2S,3S)-1,4-Dimercaptobutane-2,3-diol), more commonly known as DTT (dithiothreitol), is also present within the structure. This molecule is responsible for protecting thiol groups from oxidation. The molecule is surrounded by water molecules as well, which form hydrogen bonds with side residues to stabilize the structure. The enzyme's structure is shown.

Mechanism of lipoyl synthase

As previously mentioned, lipoyl synthase is a member of a subfamily of the radical SAM(S-adenosyl methionine) enzyme family, which use a [4Fe-4S] cluster cofactor. This cofactor is used by this enzyme to produce 5'-deoxyadenosyl 5'-radical (5'-dA). Lipoyl synthase itself uses this radical to abstract hydrogens from the 6th and 8th carbons of the protein N6(octanoyl)lysine substrate. Two sulfurs from one of lipoyl synthase's two [4Fe-4S] clusters, known as the auxiliary cluster, are then attached to the 6th and 8th carbons in place of the abstracted hydrogens.The protein N6-(octanoyl)lysine substrate is then converted into the protein N6-(lipoyl)lysine. The figure on the right depicts the lysine interacting with the auxiliary cluster to add one sulfur, which then becomes an [4Fe-3S] cluster. The other [4Fe-4S] cluster is coordinated by the radical SAM motif of the enzyme (CxxxCxxC) and participates in radical SAM characteristic chemistry to activate the substrate for subsequent sulfur insertion. The three substrates of this enzyme are N6-(octanoyl)lysine, sulfur, and S-adenosyl-L-methionine. The three products are N6-(lipoyl)lysine, L-methionine, and 5'-deoxyadenosine. Below displays the overall reaction catalyzed by lipoyl synthase, with the structures of each substrate and product.

Importance of lipoyl synthase This enzyme participates in lipoic acid metabolism, where it performs the final step in lipoic acid biosynthesis. Lipoic acid is a cofactor that has different functions within different organisms. The lipoic acid generation in yeast cells increases the number of divisions in the cells as well as protects yeast cells from hydrogen peroxide. Lipoic acid is an important co-factor in many enzyme systems, and one of them is the pyruvate dehydrogenase complex. Studies that repressed the function of lipoyl synthase in Arabidopsis thaliana seeds showed that this did not have adverse effects on seed growth and weight, but shortened the generation time as well as the flowering time of the plants. Repression resulted in earlier flowering times and decreased the generation times between seeds by almost 10%.

Possible side effects of lipoyl synthase in plants Overexpression of this enzyme in sunflower plants has been found to eventually sequester the amount of SAM present in transgenic Arabidopsis plants. SAM is a molecule that is required in other enzymatic complexes found in this plant as well, as well as the overall structure of the plant, so this sequestration may cause a reduction in the fatty acid biosynthesis in the Arabidopsis seeds.

References

Illustrations

Lipoyl synthase: This image displays the crystal structure of M. tuberculosis lipoyl synthase. The 11 α-helices are displayed in red and the 7 β sheets are displayed in blue. The DTV cofactor is displayed in yellow. The two [4Fe-4S] clusters are displayed as cubic structures within the enzyme. PBD Code: 5EXI
This image displays the crystal structure of M. tuberculosis lipoyl synthase. The 11 α-helices are displayed in red and the 7 β sheets are displayed in blue. The DTV cofactor is displayed in yellow. The two [4Fe-4S] clusters are displayed as cubic structures within the enzyme. PBD Code: 5EXI
Lipoyl synthase: This image displays the auxillery [4Fe-4S] cluster adding a sulfur onto a lysine residue that is part of the protein. This causes the cluster to become [4Fe-3S] and the modified lysine is formed (labeled XOK). The 5'-deoxyadenosine is also pictured, along with the coordinate cysteine residues . PBD Code: 5EXK
This image displays the auxillery [4Fe-4S] cluster adding a sulfur onto a lysine residue that is part of the protein. This causes the cluster to become [4Fe-3S] and the modified lysine is formed (labeled XOK). The 5'-deoxyadenosine is also pictured, along with the coordinate cysteine residues . PBD Code: 5EXK
Lipoyl synthase: This image depicts the enzyme catalyzed reaction involving lipoyl synthase. The lysine is a residue a part of the polypeptide backbone of the protein. The sulfur molecules comes from the [4Fe-4S] auxiliary cluster.
This image depicts the enzyme catalyzed reaction involving lipoyl synthase. The lysine is a residue a part of the polypeptide backbone of the protein. The sulfur molecules comes from the [4Fe-4S] auxiliary cluster.

Worked examples

Example 1 — a first encounter with Lipoyl synthase

Start with the simplest possible case. Write down what Lipoyl synthase claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In engineering, 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 Lipoyl synthase 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 Lipoyl synthase 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 Lipoyl synthase

In research
Lipoyl synthase appears in engineering 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 Lipoyl synthase 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
Lipoyl synthase is common in secondary-school and first-year university syllabi. It links to neighbouring topics EC 2.8.1, Enzymes of unknown structure, so understanding it makes those chapters shorter.
In everyday life
Look for Lipoyl synthase 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.

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How to study Lipoyl synthase in 20 minutes

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

Frequently asked questions

What is Lipoyl synthase in simple terms?

Lipoyl synthase is an enzyme that belongs to the radical SAM (S-adenosyl methionine) family. Within the radical SAM superfamily, lipoyl synthase is in a sub-family of enzymes that catalyze sulfur insertion reactions.

Why does Lipoyl synthase matter?

Because it connects several engineering 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 Lipoyl synthase?

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 Lipoyl synthase.

Tags

  • EC 2.8.1
  • Enzymes of unknown structure

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