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4cd2

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Revision as of 06:38, 4 April 2018

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

Structural highlights

4cd2 is a 1 chain structure with sequence from Pneca. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1cd2, 2cd2, 3cd2
Activity:	Dihydrofolate reductase, with EC number 1.5.1.3
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[DYR_PNECA] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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 >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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Cody V, Galitsky N, Rak D, Luft JR, Pangborn W, Queener SF. Ligand-induced conformational changes in the crystal structures of Pneumocystis carinii dihydrofolate reductase complexes with folate and NADP+. Biochemistry. 1999 Apr 6;38(14):4303-12. PMID:10194348 doi:10.1021/bi982728m

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4cd2"

@@ Line 1: / Line 1: @@
 ==LIGAND INDUCED CONFORMATIONAL CHANGES IN THE CRYSTAL STRUCTURES OF PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE COMPLEXES WITH FOLATE AND NADP+==
 <StructureSection load='4cd2' size='340' side='right' caption='[[4cd2]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1cd2|1cd2]], [[2cd2|2cd2]], [[3cd2|3cd2]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4cd2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cd2 OCA], [http://pdbe.org/4cd2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cd2 RCSB], [http://www.ebi.ac.uk/pdbsum/4cd2 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4cd2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cd2 OCA], [http://pdbe.org/4cd2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cd2 RCSB], [http://www.ebi.ac.uk/pdbsum/4cd2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cd2 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cd/4cd2_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cd/4cd2_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

4cd2

From Proteopedia

Revision as of 06:38, 4 April 2018

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

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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