1zly

From Proteopedia

(Difference between revisions)

Revision as of 09:06, 20 January 2021

The structure of human glycinamide ribonucleotide transformylase in complex with alpha,beta-N-(hydroxyacetyl)-D-ribofuranosylamine and 10-formyl-5,8,dideazafolate

Structural highlights

1zly 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:	,
Related:	1meo, 1mej, 1men, 1njs, 1zlx
Gene:	GART, PRGS (HUMAN)
Activity:	Phosphoribosylglycinamide formyltransferase, with EC number 2.1.2.2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

Glycinamide ribonucleotide transformylase (GART; 10-formyltetrahydrofolate:5'-phosphoribosylglycinamide formyltransferase, EC 2.1.2.2), an essential enzyme in de novo purine biosynthesis, has been a chemotherapeutic target for several decades. The three-dimensional structure of the GART domain from the human trifunctional enzyme has been solved by X-ray crystallography. Models of the apoenzyme, and a ternary complex with the 10-formyl-5,8-dideazafolate cosubstrate and a glycinamide ribonucleotide analogue, hydroxyacetamide ribonucleotide [alpha,beta-N-(hydroxyacetyl)-d-ribofuranosylamine], are reported to 2.2 and 2.07 A, respectively. The model of the apoenzyme represents the first structure of GART, from any source, with a completely unoccupied substrate and cosubstrate site, while the ternary complex is the first structure of the human GART domain that is bound at both the substrate and cosubstrate sites. A comparison of the two models therefore reveals subtle structural differences that reflect substrate and cosubstrate binding effects and implies roles for the invariant residues Gly 133, Gly 146, and His 137. Preactivation of the DDF formyl group appears to be key for catalysis, and structural flexibility of the active end of the substrate may facilitate nucleophilic attack. A change in pH, rather than folate binding, correlates with movement of the folate binding loop, whereas the phosphate binding loop position does not vary with pH. The electrostatic surface potentials of the human GART domain and Escherichia coli enzyme explain differences in the binding affinity of polyglutamylated folates, and these differences have implications to future chemotherapeutic agent design.

The apo and ternary complex structures of a chemotherapeutic target: human glycinamide ribonucleotide transformylase.,Dahms TE, Sainz G, Giroux EL, Caperelli CA, Smith JL Biochemistry. 2005 Jul 26;44(29):9841-50. PMID:16026156^[1]

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

References

↑ Dahms TE, Sainz G, Giroux EL, Caperelli CA, Smith JL. The apo and ternary complex structures of a chemotherapeutic target: human glycinamide ribonucleotide transformylase. Biochemistry. 2005 Jul 26;44(29):9841-50. PMID:16026156 doi:10.1021/bi050307g

1 Structural highlights
2 Evolutionary Conservation
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/1zly"

@@ Line 1: / Line 1: @@
 ==The structure of human glycinamide ribonucleotide transformylase in complex with alpha,beta-N-(hydroxyacetyl)-D-ribofuranosylamine and 10-formyl-5,8,dideazafolate==
-<StructureSection load='1zly' size='340' side='right' caption='[[1zly]], [[Resolution|resolution]] 2.07&Aring;' scene=''>
+<StructureSection load='1zly' size='340' side='right'caption='[[1zly]], [[Resolution|resolution]] 2.07&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1zly]] 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=1ZLY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ZLY FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1zly]] 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=1ZLY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1ZLY FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DQB:4-[(4-{[(2-AMINO-4-OXO-3,4-DIHYDROQUINAZOLIN-6-YL)METHYL]AMINO}BENZOYL)AMINO]BUTANOIC+ACID'>DQB</scene>, <scene name='pdbligand=GRF:5-O-PHOSPHONO-BETA-D-RIBOFURANOSYLAMINE'>GRF</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DQB:4-[(4-{[(2-AMINO-4-OXO-3,4-DIHYDROQUINAZOLIN-6-YL)METHYL]AMINO}BENZOYL)AMINO]BUTANOIC+ACID'>DQB</scene>, <scene name='pdbligand=GRF:5-O-PHOSPHONO-BETA-D-RIBOFURANOSYLAMINE'>GRF</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1meo|1meo]], [[1mej|1mej]], [[1men|1men]], [[1njs|1njs]], [[1zlx|1zlx]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1meo|1meo]], [[1mej|1mej]], [[1men|1men]], [[1njs|1njs]], [[1zlx|1zlx]]</div></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GART, PRGS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoribosylglycinamide_formyltransferase Phosphoribosylglycinamide formyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.2.2 2.1.2.2] </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=1zly FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zly OCA], [http://pdbe.org/1zly PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1zly RCSB], [http://www.ebi.ac.uk/pdbsum/1zly PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1zly ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1zly FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zly OCA], [http://pdbe.org/1zly PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1zly RCSB], [http://www.ebi.ac.uk/pdbsum/1zly PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1zly ProSAT]</span></td></tr>
 </table>
 == Evolutionary Conservation ==
@@ Line 34: / Line 34: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Phosphoribosylglycinamide formyltransferase]]
 [[Category: Caperelli, C A]]

1zly

From Proteopedia

Revision as of 09:06, 20 January 2021

The structure of human glycinamide ribonucleotide transformylase in complex with alpha,beta-N-(hydroxyacetyl)-D-ribofuranosylamine and 10-formyl-5,8,dideazafolate

Structural highlights

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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