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| - | [[Image:2inq.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:2inq.png|left|200px]] |
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| | {{STRUCTURE_2inq| PDB=2inq | SCENE= }} | | {{STRUCTURE_2inq| PDB=2inq | SCENE= }} |
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| - | '''Neutron Crystal Structure of Escherichia coli Dihydrofolate Reductase Bound to the Anti-cancer drug, Methotrexate'''
| + | ===Neutron Crystal Structure of Escherichia coli Dihydrofolate Reductase Bound to the Anti-cancer drug, Methotrexate=== |
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| - | ==Overview==
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| - | Hydrogen atoms play a central role in many biochemical processes yet are difficult to visualize by x-ray crystallography. Spallation neutron sources provide a new arena for protein crystallography with TOF measurements enhancing data collection efficiency and allowing hydrogen atoms to be located in smaller crystals of larger biological macromolecules. Here we report a 2.2-A resolution neutron structure of Escherichia coli dihydrofolate reductase (DHFR) in complex with methotrexate (MTX). Neutron data were collected on a 0.3-mm(3) D(2)O-soaked crystal at the Los Alamos Neutron Scattering Center. This study provides an example of using spallation neutrons to study protein dynamics, to identify protonation states directly from nuclear density maps, and to analyze solvent structure. Our structure reveals that the occluded loop conformation [monomer (mon.) A] of the DHFR.MTX complex undergoes greater H/D exchange compared with the closed-loop conformer (mon. B), partly because the Met-20 and beta(F-G) loops readily exchange in mon. A. The eight-stranded beta sheet of both DHFR molecules resists H/D exchange more than the helices and loops. However, the C-terminal strand, betaH, in mon. A is almost fully exchanged. Several D(2)Os form hydrogen bonds with exchanged amides. At the active site, the N1 atom of MTX is protonated and thus charged when bound to DHFR. Several D(2)Os are observed at hydrophobic surfaces, including two pockets near the MTX-binding site. A previously unidentified D(2)O hydrogen bonds with the catalytic D27 in mon. B, stabilizing its negative charge.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_17130456}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17130456 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_17130456}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Nucleotide binding domain]] | | [[Category: Nucleotide binding domain]] |
| | [[Category: Pseudo-rossman fold]] | | [[Category: Pseudo-rossman fold]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 07:41:35 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 22:53:27 2008'' |
Revision as of 19:53, 27 July 2008
Template:STRUCTURE 2inq
Neutron Crystal Structure of Escherichia coli Dihydrofolate Reductase Bound to the Anti-cancer drug, Methotrexate
Template:ABSTRACT PUBMED 17130456
About this Structure
2INQ is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
Neutron diffraction studies of Escherichia coli dihydrofolate reductase complexed with methotrexate., Bennett B, Langan P, Coates L, Mustyakimov M, Schoenborn B, Howell EE, Dealwis C, Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18493-8. Epub 2006 Nov 27. PMID:17130456
Page seeded by OCA on Sun Jul 27 22:53:27 2008
