Introduction

The two protein subunits possess dense regions of Main points: - introduce general characteristics of protein (location within cell, substrate activity, relation to cysteamine) - A small paragraph on its discovery - The broad impact of the protein (what happens if it loses function?)

Overall Structure

- 506 total residues, 87 missing - Two chains, each with many alpha helices and beta sheets - 43 missing residues: 8-20, 484-513 - Chain B 44 missing residues: 8-20, 484-513

Ligands and non-standard residues

- 2 RRV - 2 PEG - 8 NAG

Binding Interactions

4CYG is a key protein that is involved in the breakdown of pantetheine to panthothenic acid and cysteamine. These proteins are associated with many metabolic diseases like type 2 diabetes. Understanding the binding interaction would give insight into treating these diseases more effectively. 4CYG has three (Glu79, Lys178 and Cys211) that represents the active site of the enzyme. The purple amino acids represent the three amino acids directly involved in the binding interactions. The active site is located in the center of the enzyme in between the two sub-units. It was discovered that Glu79 and Lys178 were responsible for orienting and activating Cys211 to catalyze the reaction. The substrate forms a covalent bond with Cys211 producing the transition state.[1]

In addition, the two residues are essential for enzymatic function too. The purple regions are polar whereas the grey regions are hydrophobic. The two black amino acids represent GLU249 and GLU439. The two glutamic acid residues are both located in hydrophobic regions 4 Angstroms away. Although this is energetically unfavorable to have a polar amino acid in a nonpolar region, these two amino acids help maintain the structure between the two sub-units for proper binding interactions to occur.[1]

Additional Features

The biological importance of Pantetheinase is found in the products Cysteamine and vitamin B5, formed from the hydrolysis reaction shown below. Cysteamine and Vitamin B5 are key components in the synthesis of other necessary biomolecules such as acetylcholine and Coenzyme A respectively.

Inhibition

The importance of Pantetheinase stems from the vitality of the components of the reaction it catalyzes. It is for this reason that Pantetheinase has been a promising point of research in the medical field. Pantetheine analogues known as pantothenamides have been shown to act as effective antibiotics that protect the body from bacterial intruders. The similarity of these analogues to Pantetheine allow for the active sites of pantetheinase to catalyze their breakdown through hydrolysis. The administration of RR6 in the presence of pantetheinase and other antibiotic pantothenamides revealed that RR6 acts as a competitive inhibitor with great affinity for the active sites on pantetheinase, thus preserving desired concentrations of the pantothenamides with antibiotic characteristics.

The purple chains represent the polar and therefore hydrophilic regions of 4CYG and the grey chains represent the nonpolar hydrophobic regions of .

Quiz Question 1

- Additional research needed to formulate question (may potentially pertain to structure-substrate interaction)

See Also

• 1h1t
• 1mop
• 1esm

Credits

Introduction - Patrick Tonne

Overall Structure - Luke Schnitzler

Drug Binding Site - Owen O'Connor

Additional Features - Nick Saint

Quiz Question 1 - Tyler Russell

References

1. ↑ Boersma YL, Newman J, Adams TE, Cowieson N, Krippner G, Bozaoglu K, Peat TS. The structure of vanin 1: a key enzyme linking metabolic disease and inflammation. Acta Crystallogr D Biol Crystallogr. 2014 Dec 1;70(Pt 12):3320-9. doi:, 10.1107/S1399004714022767. Epub 2014 Nov 28. PMID:25478849 doi:http://dx.doi.org/10.1107/S1399004714022767