A Structured-based Model for the Decreased Activity of Ala222Val and Glu429Ala Methylenetetrahydrofolate Reductase (MTHFR) Mutants

BACK TO CONTENTS | PDF | PREVIOUS | NEXT

Title	A Structured-based Model for the Decreased Activity of Ala222Val and Glu429Ala Methylenetetrahydrofolate Reductase (MTHFR) Mutants
Authors	Khuram Shahzad^1,2, Abdul Hai³, Asifa Ahmed², Nadeem Kizilbash³* & Jamal Alruwaili³
Affiliation	¹Illinois Informatics Institute, University of Illinois, Urbana-Champaign, Illinois, U.S.A; ²Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan; ³Department of Biochemistry, Faculty of Medicine & Applied Medical Sciences, Northern Border University, Arar-91431, Saudi Arabia
Email	fsd707@gmail.com; *Corresponding author
Article Type	Hypothesis
Date	Received September 23, 2013; Accepted September 30, 2013; Published November 11, 2013
Abstract	The structure of human Methylenetetrahydrofolate Reductase (MTHFR) is not known either by NMR or by X-ray methods. Phosphorylation seems to play an important role in the functioning of this flavoprotein. MTHFR catalyzes an irreversible reaction in homocysteine metabolism. Phosphorylation decreases the activity of MTHFR by enhancing the sensitivity of the enzyme to S-Adenosylmethione. Two common polymorphisms in MTHFR, Ala222Val and Glu429Ala, can result in a number of vascular diseases. Effects of the Glu429Ala polymorphism on the structure of human MTHFR remain undetermined due to limited structural information. Hence, structural models of the MTHFR mutants were constructed using I-TASSER and assessed by PROCHECK, DFIRE and Verify3D tools. A mechanism is further suggested for the decreased activity of the Ala222Val and Glu429Ala mutants due to a decrease in number of serine phosphorylation sites using information gleaned from the molecular models. This provides insights for the understanding of structure-function relationship for MTHFR.
Keywords	Methylenetetrahydrofolate Reductase, in silico modeling, hyperhomocysteinemia, 5,10-Methylenetetrahydrofolate, Methylenetetrahydrofolate Reductase phosphorylation.
Citation	Shahzad et al. Bioinformation 9(18): 929-936 (2013)
Edited by	P Kangueane
ISSN	0973-2063
Publisher	Biomedical Informatics
License	This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.