Sandbox Reserved 434

This Sandbox is Reserved from January 19, 2016, through August 31, 2016 for use for Proteopedia Team Projects by the class Chemistry 423 Biochemistry for Chemists taught by Lynmarie K Thompson at University of Massachusetts Amherst, USA. This reservation includes Sandbox Reserved 425 through Sandbox Reserved 439.

Pantetheinase (4CYG)

by [Luke Schnitzler, Patrick Tonne, Owen O'Connor, Tyler Russell, Nicholas Sant]

Student Projects for UMass Chemistry 423 Spring 2016 <StructureSection load='4CYG' size='350' side='right' caption='caption for Molecular Playground (PDB entry 4CYG)' scene=>

Introduction

The two protein subunits possess dense regions of beta strands and alpha helices. 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 - Chain A, colored by component 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 Catalytic Residues (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 GLU249 AND GLU439 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 purple chains represent the polar and therefore hydrophilic regions of 4CYG and the grey chains represent the nonpolar hydrophobic regions of 4CYG.

The biological importance of Pantetheinase is evident as the products of the hydrolysis reaction, cysteamine and vitamin B5, are key components in the synthesis of other necessary biomolecules such as acetylcholine and Coenzyme A respectively.

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