4cd2

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[[Image:4cd2.gif|left|200px]]
 
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==LIGAND INDUCED CONFORMATIONAL CHANGES IN THE CRYSTAL STRUCTURES OF PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE COMPLEXES WITH FOLATE AND NADP+==
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The line below this paragraph, containing "STRUCTURE_4cd2", creates the "Structure Box" on the page.
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<StructureSection load='4cd2' size='340' side='right'caption='[[4cd2]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[4cd2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pneumocystis_carinii Pneumocystis carinii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CD2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CD2 FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FOL:FOLIC+ACID'>FOL</scene></td></tr>
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{{STRUCTURE_4cd2| PDB=4cd2 | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4cd2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cd2 OCA], [https://pdbe.org/4cd2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cd2 RCSB], [https://www.ebi.ac.uk/pdbsum/4cd2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cd2 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/DYR_PNECA DYR_PNECA] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cd/4cd2_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=4cd2 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Structural data from two independent crystal forms (P212121 and P21) of the folate (FA) binary complex and from the ternary complex with the oxidized coenzyme, NADP+, and recombinant Pneumocystis carinii dihydrofolate reductase (pcDHFR) refined to an average of 2.15 A resolution, show the first evidence of ligand-induced conformational changes in the structure of pcDHFR. These data are also compared with the crystal structure of the ternary complex of methotrexate (MTX) with NADPH and pcDHFR in the monoclinic lattice with data to 2.5 A resolution. Comparison of the data for the FA binary complex of pcDHFR with those for the ternary structures reveals significant differences, with a &gt;7 A movement of the loop region near residue 23 that results in a new "flap-open" position for the binary complex, and a "closed" position in the ternary complexes, similar to that reported for Escherichia coli (ec) DHFR complexes. In the orthorhombic lattice for the binary FA pcDHFR complex, there is also an unwinding of a short helical region near residue 47 that places hydrophobic residues Phe-46 and Phe-49 toward the outer surface, a conformation that is stabilized by intermolecular packing contacts. The pyrophosphate moiety of NADP+ in the ternary folate pcDHFR complexes shows significant differences in conformation compared with that observed in the MTX-NADPH-pcDHFR ternary complex. Additionally, comparison of the conformations among these four pcDHFR structures reveals evidence for subdomain movement that correlates with cofactor binding states. The larger binding site access in the new "flap-open" loop 23 conformation of the binary FA complex is consistent with the rapid release of cofactor from the product complex during catalysis as well as the more rapid release of substrate product from the binary complex as a result of the weaker contacts of the closed loop 23 conformation, compared to ecDHFR.
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'''LIGAND INDUCED CONFORMATIONAL CHANGES IN THE CRYSTAL STRUCTURES OF PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE COMPLEXES WITH FOLATE AND NADP+'''
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Ligand-induced conformational changes in the crystal structures of Pneumocystis carinii dihydrofolate reductase complexes with folate and NADP+.,Cody V, Galitsky N, Rak D, Luft JR, Pangborn W, Queener SF Biochemistry. 1999 Apr 6;38(14):4303-12. PMID:10194348<ref>PMID:10194348</ref>
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==Overview==
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Structural data from two independent crystal forms (P212121 and P21) of the folate (FA) binary complex and from the ternary complex with the oxidized coenzyme, NADP+, and recombinant Pneumocystis carinii dihydrofolate reductase (pcDHFR) refined to an average of 2.15 A resolution, show the first evidence of ligand-induced conformational changes in the structure of pcDHFR. These data are also compared with the crystal structure of the ternary complex of methotrexate (MTX) with NADPH and pcDHFR in the monoclinic lattice with data to 2.5 A resolution. Comparison of the data for the FA binary complex of pcDHFR with those for the ternary structures reveals significant differences, with a &gt;7 A movement of the loop region near residue 23 that results in a new "flap-open" position for the binary complex, and a "closed" position in the ternary complexes, similar to that reported for Escherichia coli (ec) DHFR complexes. In the orthorhombic lattice for the binary FA pcDHFR complex, there is also an unwinding of a short helical region near residue 47 that places hydrophobic residues Phe-46 and Phe-49 toward the outer surface, a conformation that is stabilized by intermolecular packing contacts. The pyrophosphate moiety of NADP+ in the ternary folate pcDHFR complexes shows significant differences in conformation compared with that observed in the MTX-NADPH-pcDHFR ternary complex. Additionally, comparison of the conformations among these four pcDHFR structures reveals evidence for subdomain movement that correlates with cofactor binding states. The larger binding site access in the new "flap-open" loop 23 conformation of the binary FA complex is consistent with the rapid release of cofactor from the product complex during catalysis as well as the more rapid release of substrate product from the binary complex as a result of the weaker contacts of the closed loop 23 conformation, compared to ecDHFR.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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4CD2 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Pneumocystis_carinii Pneumocystis carinii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CD2 OCA].
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</div>
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<div class="pdbe-citations 4cd2" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Ligand-induced conformational changes in the crystal structures of Pneumocystis carinii dihydrofolate reductase complexes with folate and NADP+., Cody V, Galitsky N, Rak D, Luft JR, Pangborn W, Queener SF, Biochemistry. 1999 Apr 6;38(14):4303-12. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10194348 10194348]
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*[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]]
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[[Category: Dihydrofolate reductase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Pneumocystis carinii]]
[[Category: Pneumocystis carinii]]
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[[Category: Single protein]]
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[[Category: Cody V]]
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[[Category: Cody, V.]]
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[[Category: Galitsky N]]
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[[Category: Galitsky, N.]]
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[[Category: Luft JR]]
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[[Category: Luft, J R.]]
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[[Category: Pangborn W]]
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[[Category: Pangborn, W.]]
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[[Category: Queener SF]]
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[[Category: Queener, S F.]]
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[[Category: Rak D]]
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[[Category: Rak, D.]]
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[[Category: Folate]]
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[[Category: Oxido-reductase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 22:21:53 2008''
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Current revision

LIGAND INDUCED CONFORMATIONAL CHANGES IN THE CRYSTAL STRUCTURES OF PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE COMPLEXES WITH FOLATE AND NADP+

PDB ID 4cd2

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