Comparison and correlation of binding mode of ATP in the kinase domains of Hexokinase family.

Yellapu Nanda Kumar,Gopal Sowjenya,Uppu Venkateswara Prasad,Pasupuleti Santhosh Kumar,Valasani Koteswara Rao,Matcha Bhaskar,Pvgk Sarma,Jangampalli Adi Pradeepkiran,Sthanikam Yeswanth

doi:10.6026/97320630008543

Abstract

Hexokinases (HKs) are the enzymes that catalyses the ATP dependent phosphorylation of Hexose sugars to Hexose-6-Phosphate (Hex-6-P). There exist four different forms of HKs namely HK-I, HK-II, HK-III and HK-IV and all of them share a common ATP binding site core surrounded by more variable sequence that determine substrate affinities. Although they share a common binding site but they differ in their kinetic functions, hence the present study is aimed to analyze the binding mode of ATP. The analysis revealed that the four ATP binding domains are showing 13 identical, 7 similar and 6 dissimilar residues with similar structural conformation. Molecular docking of ATP into the kinase domains using Molecular Operating Environment (MOE) soft ware tool clearly showed the variation in the binding mode of ATP with variable docking scores. This probably explains the variable phosphorylation rates among hexokinases family.

Highlights

HK catalyzes the phosphorylation process by transferring the γphosphoryl group from ATP to the OH group of sixth carbon of Hexose sugars to give Hex-6-P
HK-I is predominantly present in brain and kidney and HK-II is predominant in skeletal muscle and epididymal fat pad [2]
HK-I and HK-II have a tail on the N-terminus that is important to bind with mitochondria whereas, HK-III and HK-IV lacks such structures and they are unable to bind to mitochondria

Summary

Introduction

HK catalyzes the phosphorylation process by transferring the γphosphoryl group from ATP to the OH group of sixth carbon of Hexose sugars to give Hex-6-P. HK-I and HK-II have a tail on the N-terminus that is important to bind with mitochondria whereas, HK-III and HK-IV lacks such structures and they are unable to bind to mitochondria. These isozymes may be associated with metabolic pathways other than glycolysis. All HKs share a common ATP binding site core surrounded by more variable sequence that determines substrate affinities. They share a common ATP binding site, the difference in their kinetic functions was observed [4]. This may be probably due to the variation in the active site residues and conformations which will affect

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Conclusion