Hexokinase
Induced Fit and Hexokinase

Hexokinase

Flash Tutorial:

Fig.1 Glycolysis and Hexokinase
Hexokinase
Fig.2 Induced Fit Movie

Lehninger’s definition of induced fit:

A change in the conformation of an enzyme in response to substrate binding that renders the enzyme catalytically active.
Fig.3 Mechanism of Phosphorylation, Catalyzed by Hexokinase
Fig.4 Lock and Key Model
Fig.5 Induced Fit Model
Fig.6 Structure of Hexokinase
Fig.7 Active Site of Glucokinase/Hexokinase

Useful Sites on the Issue:

This is the home page of Daniel E. Koshland http://mcb.berkeley.edu/faculty/BMB/koshlandd.html
(requires CHIME to observe computer graphics) This site shows the glucose binding sites of hexokinase, hydrophobic channels, and the open and closed forms of hexokinase in three dimensional diagrams. http://www.siu.edu/departments/biochem/chime_rasmol/glycolysis/hexokinase_comp.htm
(requires CHIME to observe computer graphics) This site has an interactive animation of the mechanism and conformational changes of our enzyme before and after binding of its substrate (glucose). http://www.wiley.com/legacy/college/boyer/0470003790/structure/hexokinase/hexokinase.htm
This site shows a tutorial on the induced fit model with an emphasis on the mechanism’s kinetics. http://bmbiris.bmb.uga.edu/wampler/8010/lectures/kinetics/steady/sld073.htm
This site contains not only a virtual tutorial of induced fit, but also contains links to additional bodies of information on the subject. http://resources.ed.gov.hk/biology/english/health/enzyme/enzyme_factors_inducedfit.html
This site illustrates a simple 2D animation of induced fit. It also includes how a substrate will approach and then bind to the active site of an enzyme. http://bio.winona.msus.edu/berg/ANIMTNS/ind-fit.htm
(requires CHIME to observe computer graphics) This site shows an interactive model of the enzyme hexokinase, and then Wireframe model of hexokinase. http://scholar.hw.ac.uk/site/biology/activity7.asp?outline
Here is a link to a power point slide show which contains information and images on the following topics for human brain hexokinase: biological significances, enzyme function, enzyme structure, binding site, binding mechanism, and enzyme kinetics. http://www.chem.uncc.edu/courses/6101/Lectures/Student%20Presentations/ATPBINDINGSITEOFHUMANBRAINHEXOKINASE.ppt
The Protein Data Bank’s “Molecule of the Month” picture of hexokinase and short summery explaining its significance in the first step of the glycolysis. http://www.rcsb.org/pdb/molecules/pdb50_2.html
This is a link to The Protein Families Database of Alignments under the topic of hexokinase. http://www.sanger.ac.uk/cgi-bin/Pfam/getacc?PF00349

Scientific Publications:

“Glucose-Induced Conformational Change in Yeast Hexokinase” W S Bennett, Jr and T A Steitz; Proceedings of the National Academy of Sciences of the United States of America, 1978, vol. 75: 4848–4852 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=336218
“The Key-Lock Theory and the Induced Fit Theory” Daniel E. Koshland, Jr.; Chemistry International Education England, 1994, vol. 33: 2375-2378 http://www.tulane.edu/~biochem/lecture/gbch701/koshland2.pdf
“Conformational Changes of Proteins Arising From Normal Mode Calculations” F. Tama and Y.-H. Sanejouand; Protein Engineering, 2001, vol. 14: 1-6 http://www.tulane.edu/~biochem/lecture/gbch701/koshland2.pdf
“Induced Fit in Guanidino kinases—Comparison of Substrate-Free and Transition State Analog Structures of Arginine Kinase” Mohammad S. Yousef, Shawn A. Clark, Pamela K. Pruett, Thayumanasamy Somasundaram, W. Ross Ellington, and Michael S. Chapman; Protein Science, 2003, vol. 12: 103-111 http://www.proteinscience.org/cgi/content/full/12/1/103
“Proteomics and Models for Enzyme Cooperativity” Daniel E. Koshland Jr. and Kambiz Hamadani; Journal of Biological Chemistry, 2002, vol. 277: 46841-46844 http://www.jbc.org/cgi/content/full/277/49/46841
“Structural Model of Human Glucokinase in Complex With Glucose and ATP” Bhuvaneshwari Mahalingam, Antonio Cuesta-Munoz, Elizabeth A. Davis, Franz M. Matschinsky, Robert W. Harrison, and Irene T. Weber; Diabetes, 1999, vol. 48: 1698-1705 http://diabetes.diabetesjournals.org/cgi/reprint/48/9/1698