This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

6hfd

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

Human dihydroorotase mutant F1563L apo structure

Structural highlights

6hfd is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Gene:	CAD (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PYR1_HUMAN] This protein is a "fusion" protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase).

Publication Abstract from PubMed

The dihydroorotase (DHOase) domain of the multifunctional protein carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase (CAD) catalyzes the third step in the de novo biosynthesis of pyrimidine nucleotides in animals. The crystal structure of the DHOase domain of human CAD (huDHOase) revealed that, despite evolutionary divergence, its active site components are highly conserved with those in bacterial DHOases, encoded as monofunctional enzymes. An important element for catalysis, conserved from Escherichia coli to humans, is a flexible loop that closes as a lid over the active site. Here, we combined mutagenic, structural, biochemical, and molecular dynamics analyses to characterize the function of the flexible loop in the activity of CAD's DHOase domain. A huDHOase chimera bearing the E. coli DHOase flexible loop was inactive, suggesting the presence of distinctive elements in the flexible loop of huDHOase that cannot be replaced by the bacterial sequence. We pinpoint Phe-1563, a residue absolutely conserved at the tip of the flexible loop in CAD's DHOase domain, as a critical element for the conformational equilibrium between the two catalytic states of the protein. Substitutions of Phe-1563 with Ala, Leu or Thr prevented the closure of the flexible loop and inactivated the protein, whereas substitution with Tyr enhanced the interactions of the loop in the closed position and reduced fluctuations and the reaction rate. Our results confirm the importance of the flexible loop in CAD's DHOase domain and explain the key role of Phe-1563 in configuring the active site and in promoting substrate strain and catalysis.

Characterization of the catalytic flexible loop in the dihydroorotase domain of the human multi-enzymatic protein CAD.,Del Cano-Ochoa F, Grande-Garcia A, Reverte-Lopez M, D'Abramo M, Ramon-Maiques S J Biol Chem. 2018 Oct 12. pii: RA118.005494. doi: 10.1074/jbc.RA118.005494. PMID:30315107^[1]

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

References

↑ Del Cano-Ochoa F, Grande-Garcia A, Reverte-Lopez M, D'Abramo M, Ramon-Maiques S. Characterization of the catalytic flexible loop in the dihydroorotase domain of the human multi-enzymatic protein CAD. J Biol Chem. 2018 Oct 12. pii: RA118.005494. doi: 10.1074/jbc.RA118.005494. PMID:30315107 doi:http://dx.doi.org/10.1074/jbc.RA118.005494

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6hfd"

@@ Line 3: / Line 3: @@
 <StructureSection load='6hfd' size='340' side='right' caption='[[6hfd]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6hfd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HFD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HFD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6hfd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HFD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HFD FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CAD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6hfd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hfd OCA], [http://pdbe.org/6hfd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hfd RCSB], [http://www.ebi.ac.uk/pdbsum/6hfd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hfd ProSAT]</span></td></tr>
 </table>
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Garcia, A Grande]]
 [[Category: Ramon-Maiques, S]]

6hfd

From Proteopedia

Current revision

Human dihydroorotase mutant F1563L apo structure

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox