HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 13, 9923-9931, March 30, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/13/9923    most recent M610678200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nishimasu, H. Articles by Wakagi, T. Search for Related Content PubMed PubMed Citation Articles by Nishimasu, H. Articles by Wakagi, T. Social Bookmarking                      What's this?

Crystal Structures of an ATP-dependent Hexokinase with Broad Substrate Specificity from the Hyperthermophilic Archaeon Sulfolobus tokodaii^*

From the Department of Biotechnology, the University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan

Hexokinase catalyzes the phosphorylation of glucose to glucose 6-phosphate by using ATP as a phosphoryl donor. Recently, we identified and characterized an ATP-dependent hexokinase (StHK) from the hyperthermophilic archaeon Sulfolobus tokodaii, which can phosphorylate a broad range of sugar substrates, including glucose, mannose, glucosamine, and N-acetylglucosamine. Here we present the crystal structures of StHK in four different forms: (i) apo-form, (ii) binary complex with glucose, (iii) binary complex with ADP, and (iv) quaternary complex with xylose, Mg²⁺, and ADP. Forms i and iii are in the open state, and forms ii and iv are in the closed state, indicating that sugar binding induces a large conformational change, whereas ADP binding does not. The four different crystal structures of the same enzyme provide "snapshots" of the conformational changes during the catalytic cycle. StHK exhibits a core fold characteristic of the hexokinase family, but the structures of several loop regions responsible for substrate binding are significantly different from those of other known hexokinase family members. Structural comparison of StHK with human N-acetylglucosamine kinase and other hexokinases provides an explanation for the ability of StHK to phosphorylate both glucose and N-acetylglucosamine. A Mg²⁺ ion and coordinating water molecules are well defined in the electron density of the quaternary complex structure. This structure represents the first direct visualization of the binding mode for magnesium to hexokinase and thus allows for a better understanding of the catalytic mechanism proposed for the entire hexokinase family.

Received for publication, November 17, 2006 , and in revised form, December 27, 2006.

The atomic coordinates and structure factors (code 2E2N, 2E2O, 2E2P, and 2E2Q) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

^* This work was supported by Research Fellowship of the Japan Society for the Promotion of Science for Young Scientists 10865 (to H. N.) and the National Project on Protein Structural and Functional Analysis. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement"in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. S1 and Refs. 63 and 64.

¹ To whom correspondence should be addressed. Tel.: 81-3-5841-5152; Fax: 81-3-5841-5152; E-mail: atwakag{at}mail.ecc.u-tokyo.jp.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. A. Bonner, T. Disz, K. Hwang, J. Song, V. Vonstein, R. Overbeek, and R. A. Jensen Cohesion Group Approach for Evolutionary Analysis of TyrA, a Protein Family with Wide-Ranging Substrate Specificities Microbiol. Mol. Biol. Rev., March 1, 2008; 72(1): 13 - 53. [Abstract] [Full Text] [PDF]

				E. Reisler and E. H. Egelman Actin Structure and Function: What We Still Do Not Understand J. Biol. Chem., December 14, 2007; 282(50): 36133 - 36137. [Full Text] [PDF]