1a4i
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1a4i.gif|left|200px]] | [[Image:1a4i.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1a4i", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | | | + | or leave the SCENE parameter empty for the default display. |
| - | | | + | --> |
| - | + | {{STRUCTURE_1a4i| PDB=1a4i | SCENE= }} | |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''HUMAN TETRAHYDROFOLATE DEHYDROGENASE / CYCLOHYDROLASE''' | '''HUMAN TETRAHYDROFOLATE DEHYDROGENASE / CYCLOHYDROLASE''' | ||
| Line 29: | Line 26: | ||
[[Category: Li, Y.]] | [[Category: Li, Y.]] | ||
[[Category: Mackenzie, R E.]] | [[Category: Mackenzie, R E.]] | ||
| - | [[Category: | + | [[Category: Bifunctional]] |
| - | [[Category: | + | [[Category: Cyclohydrolase]] |
| - | [[Category: | + | [[Category: Dehydrogenase]] |
| - | [[Category: | + | [[Category: Folate]] |
| - | [[Category: | + | [[Category: Oxidoreductase]] |
| - | [[Category: | + | [[Category: Thf]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 09:48:01 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 06:48, 2 May 2008
HUMAN TETRAHYDROFOLATE DEHYDROGENASE / CYCLOHYDROLASE
Overview
BACKGROUND: The interconversion of two major folate one-carbon donors occurs through the sequential activities of NAD(P)-dependent methylene[H4]folate dehydrogenase (D) and methenyl[H4]folate cyclohydrolase (C). These activities often coexist as part of a multifunctional enzyme and there are several lines of evidence suggesting that their substrates bind at overlapping sites. Little is known, however, about the nature of this site or the identity of the active-site residues for this enzyme family. RESULTS: We have determined, to 1.5 A resolution, the structure of a dimer of the D/C domain of the human trifunctional cytosolic enzyme with bound NADP cofactor, using the MAD technique. The D/C subunit is composed of two alpha/beta domains that assemble to form a wide cleft. The cleft walls are lined with highly conserved residues and NADP is bound along one wall. The NADP-binding domain has a Rossmann fold, characterized by a modified diphosphate-binding loop fingerprint-GXSXXXG. Dimerization occurs by antiparallel interaction of two NADP-binding domains. Superposition of the two subunits indicates domain motion occurs about a well-defined hinge region. CONCLUSIONS: Analysis of the structure suggests strongly that folate-binding sites for both activities are within the cleft, providing direct support for the proposed overlapping site model. The orientation of the nicotinamide ring suggests that in the dehydrogenase-catalyzed reaction hydride transfer occurs to the pro-R side of the ring. The identity of the cyclohydrolase active site is not obvious. We propose that a conserved motif-Tyr52-X-X-X-Lys56- and/or a Ser49-Gln100-Pro102 triplet have a role in this activity.
About this Structure
1A4I is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The 3-D structure of a folate-dependent dehydrogenase/cyclohydrolase bifunctional enzyme at 1.5 A resolution., Allaire M, Li Y, MacKenzie RE, Cygler M, Structure. 1998 Feb 15;6(2):173-82. PMID:9519408 Page seeded by OCA on Fri May 2 09:48:01 2008
Categories: Homo sapiens | Single protein | Allaire, M. | Cygler, M. | Li, Y. | Mackenzie, R E. | Bifunctional | Cyclohydrolase | Dehydrogenase | Folate | Oxidoreductase | Thf
