1kmv

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1kmv.gif|left|200px]]<br /><applet load="1kmv" size="350" color="white" frame="true" align="right" spinBox="true"
+
[[Image:1kmv.gif|left|200px]]
-
caption="1kmv, resolution 1.05&Aring;" />
+
 
-
'''HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND (Z)-6-(2-[2,5-DIMETHOXYPHENYL]ETHEN-1-YL)-2,4-DIAMINO-5-METHYLPYRIDO[2,3-D]PYRIMIDINE (SRI-9662), A LIPOPHILIC ANTIFOLATE'''<br />
+
{{Structure
 +
|PDB= 1kmv |SIZE=350|CAPTION= <scene name='initialview01'>1kmv</scene>, resolution 1.05&Aring;
 +
|SITE=
 +
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=LII:(Z)-6-(2-[2,5-DIMETHOXYPHENYL]ETHEN-1-YL)-2,4-DIAMINO-5-METHYLPYRIDO[2,3-D]PYRIMIDINE'>LII</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene> and <scene name='pdbligand=DMS:DIMETHYL SULFOXIDE'>DMS</scene>
 +
|ACTIVITY= [http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3]
 +
|GENE=
 +
}}
 +
 
 +
'''HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND (Z)-6-(2-[2,5-DIMETHOXYPHENYL]ETHEN-1-YL)-2,4-DIAMINO-5-METHYLPYRIDO[2,3-D]PYRIMIDINE (SRI-9662), A LIPOPHILIC ANTIFOLATE'''
 +
 
==Overview==
==Overview==
Line 10: Line 19:
==About this Structure==
==About this Structure==
-
1KMV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=LII:'>LII</scene>, <scene name='pdbligand=NDP:'>NDP</scene> and <scene name='pdbligand=DMS:'>DMS</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KMV OCA].
+
1KMV is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KMV OCA].
==Reference==
==Reference==
-
Atomic structures of human dihydrofolate reductase complexed with NADPH and two lipophilic antifolates at 1.09 a and 1.05 a resolution., Klon AE, Heroux A, Ross LJ, Pathak V, Johnson CA, Piper JR, Borhani DW, J Mol Biol. 2002 Jul 12;320(3):677-93. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12096917 12096917]
+
Atomic structures of human dihydrofolate reductase complexed with NADPH and two lipophilic antifolates at 1.09 a and 1.05 a resolution., Klon AE, Heroux A, Ross LJ, Pathak V, Johnson CA, Piper JR, Borhani DW, J Mol Biol. 2002 Jul 12;320(3):677-93. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12096917 12096917]
[[Category: Dihydrofolate reductase]]
[[Category: Dihydrofolate reductase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
Line 28: Line 37:
[[Category: NDP]]
[[Category: NDP]]
[[Category: SO4]]
[[Category: SO4]]
-
[[Category: antiparasitic drugs]]
+
[[Category: antiparasitic drug]]
-
[[Category: lipophilic antifolates]]
+
[[Category: lipophilic antifolate]]
[[Category: oxidoreductase]]
[[Category: oxidoreductase]]
[[Category: reductase]]
[[Category: reductase]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:35:51 2008''
+
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:19:31 2008''

Revision as of 10:19, 20 March 2008

Image:1kmv.gif


PDB ID 1kmv

Drag the structure with the mouse to rotate
, resolution 1.05Å
Ligands: , , and
Activity: Dihydrofolate reductase, with EC number 1.5.1.3
Coordinates: save as pdb, mmCIF, xml



HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND (Z)-6-(2-[2,5-DIMETHOXYPHENYL]ETHEN-1-YL)-2,4-DIAMINO-5-METHYLPYRIDO[2,3-D]PYRIMIDINE (SRI-9662), A LIPOPHILIC ANTIFOLATE


Contents

Overview

The crystal structures of two human dihydrofolate reductase (hDHFR) ternary complexes, each with bound NADPH cofactor and a lipophilic antifolate inhibitor, have been determined at atomic resolution. The potent inhibitors 6-([5-quinolylamino]methyl)-2,4-diamino-5-methylpyrido[2,3-d]pyrimidine (SRI-9439) and (Z)-6-(2-[2,5-dimethoxyphenyl]ethen-1-yl)-2,4-diamino-5-methylpyrido[2,3-d ]pyrimidine (SRI-9662) were developed at Southern Research Institute against Toxoplasma gondii DHFR-thymidylate synthase. The 5-deazapteridine ring of each inhibitor adopts an unusual puckered conformation that enables the formation of identical contacts in the active site. Conversely, the quinoline and dimethoxybenzene moieties exhibit distinct binding characteristics that account for the differences in inhibitory activity. In both structures, a salt-bridge is formed between Arg70 in the active site and Glu44 from a symmetry-related molecule in the crystal lattice that mimics the binding of methotrexate to DHFR.

Disease

Known disease associated with this structure: Anemia, megaloblastic, due to DHFR deficiency (1) OMIM:[126060]

About this Structure

1KMV is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Atomic structures of human dihydrofolate reductase complexed with NADPH and two lipophilic antifolates at 1.09 a and 1.05 a resolution., Klon AE, Heroux A, Ross LJ, Pathak V, Johnson CA, Piper JR, Borhani DW, J Mol Biol. 2002 Jul 12;320(3):677-93. PMID:12096917

Page seeded by OCA on Thu Mar 20 12:19:31 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1kmv"
Personal tools