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Contents 1 Mevalonate Diphosphate Decarboxylase 1.1 Introduction 1.2 Structure 1.3 Reaction

Mevalonate Diphosphate Decarboxylase

Introduction

Mevalonate diphosphate decarboxylase (MDD) is an important enzyme required for the biosynthesis of cholesterol and other isoprenoids in mammals, bacteria, yeast and fungi ^[1]. MDD is a member of the GHMP (Galactokinase, Homoserine kinase, mevalonate kinase and phosphomevalonate kinase) enzyme family, and is responsible for the conversion of mevalonate diphosphate to isopentenyl pyrophosphate with the help of 1 ATP molecule^{[1] [2]}. Even though the kinases in the GHMP family differ in quaternary structure and ability to bind a wide variety of substrates, they share a characteristic alpha/beta fold and similar sequences ^{[1] [3]}. Some GHMP kinases exist as dimers, some as tetramers and some as monomers ^[1]. The amino acid residues in MDD are highly conserved across all species, indicating the specific important activity of the enzyme ^[1].

Template:STRUCTURE 2hk3

Structure

Mevalonate diphosphate decarboxylase exists as a symmetrical dimer^{[1] [2] [3]} . The C-terminal domains of each monomer are symmetrically oriented towards one another around a solvent-filled channel ^[1]. The dimer is stabilized between alpha helices 6 and 10 on the monomers, and also through salt bridge interactions, tyrosine and proline stacking, and hydrophobic interactions ^[1]. The interface between the monomers is very small, with only 7% of the total surface area of the monomer engaged in the interface interaction ^[2]. This small interface between monomers is a characteristic of GHMP kinases ^[2]. Each monomer consists of a single polypeptide chain with 331 amino acid residues. Each polypeptide chain has 13 alpha helices and 15 beta chains. The active site on each monomer is a deep, highly charged cleft made up seven segments of polypeptide chain, which is located away from the other monomer, and is unaffected by dimerization ^[1]. An ATP binding polypeptide segment called the P loop is also located near the active site ^[1]. A total of 19 amino acid residue side chains are involved with substrate binding in the active site ^[1].

Reaction

The mevalonate pathway encompasses 3 different enzymes that convert mevalonate to isopentenyl pyrophosphate, which is an important building block for all isoprenoids ^[4]