The New Jersey Institute of Technology's
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Title:	Structure and dynamics of soluble guanylyl cyclase
Author:	Sugino, Kentaro
View Online:	njit-etd2005-056 (xiii, 63 pages ~ 7.4 MB pdf)
Department:	Department of Computer Science
Degree:	Master of Science
Program:	Computational Biology
Document Type:	Thesis
Advisory Committee:	Ma, Qun (Committee chair) Shih, Frank Y. (Committee member) Gerbessiotis, Alexandros V. (Committee member)
Date:	2005-05
Keywords:	Soluble guanylyl cyclase 3D structure
Availability:	Unrestricted
Abstract:	Soluble guanylyl cyclase (sGC) is one of the key enzymes involved in many fundamental biological processes including vasodilatation. It can be allosterically activated by synthetic compound such as YC-l. Recently, the 3D structure of adenylyl cyclase (AC), which is a homologue of sGC, was determined. Using AC as template and homology modeling, the 3D structure of sGC is predicted. Prior experimental work has suggested two binding modes of YC- 1. In the current investigation, molecular dynamics simulations (MD) were conducted to seek more detail of molecular mechanism of sGC activation. From these MD simulations, a tentative mechanism of sGC activation is established. The difference in the initial binding modes of YC-l in its binding pocket results in different conformational changes in the active site of sGC, which results in different catalytic capability. Meanwhile, YC-l was found to be strongly attracted to α1 CYS594, a residue deep inside of the allosteric binding pocket.