View source for 4zz1


==HUMAN GAR TRANSFORMYLASE IN COMPLEX WITH GAR AND (S)-2-({4-[3-(2-AMINO-4-OXO-4,7-DIHYDRO-3H-PYRROLO[2,3-D]PYRIMIDIN-6-YL)-PROPYL]-THIOPHENE-2-CARBONYL}-AMINO)-PENTANEDIOIC ACID==
<StructureSection load='4zz1' size='340' side='right'caption='[[4zz1]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4zz1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZZ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZZ1 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.351&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3YF:(S)-2-({4-[3-(2-AMINO-4-OXO-4,7-DIHYDRO-3H-PYRROLO[2,3-D]PYRIMIDIN-6-YL)-PROPYL]-THIOPHENE-2-CARBONYL}-AMINO)-PENTANEDIOIC+ACID'>3YF</scene>, <scene name='pdbligand=GAR:GLYCINAMIDE+RIBONUCLEOTIDE'>GAR</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4zz1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zz1 OCA], [https://pdbe.org/4zz1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zz1 RCSB], [https://www.ebi.ac.uk/pdbsum/4zz1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zz1 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PUR2_HUMAN PUR2_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
2-Amino-4-oxo-6-substituted-pyrrolo[2,3-d]pyrimidine antifolate thiophene regioisomers of AGF94 (4) with a thienoyl side chain and three-carbon bridge lengths [AGF150 (5) and AGF154 (7)] were synthesized as potential antitumor agents. These analogues inhibited proliferation of Chinese hamster ovary (CHO) sublines expressing folate receptors (FRs) alpha or beta (IC50s &lt; 1 nM) or the proton-coupled folate transporter (PCFT) (IC50 &lt; 7 nM). Compounds 5 and 7 inhibited KB, IGROV1, and SKOV3 human tumor cells at subnanomolar concentrations, reflecting both FRalpha and PCFT uptake. AGF152 (6) and AGF163 (8), 2,4-diamino-5-substituted-furo[2,3-d]pyrimidine thiophene regioisomers, also inhibited growth of FR-expressing CHO and KB cells. All four analogues inhibited glycinamide ribonucleotide formyltransferase (GARFTase). Crystal structures of human GARFTase complexed with 5 and 7 were reported. In severe combined immunodeficient mice bearing SKOV3 tumors, 7 was efficacious. The selectivity of these compounds for PCFT and for FRalpha and beta over the ubiquitously expressed reduced folate carrier is a paradigm for selective tumor targeting.

6-Substituted Pyrrolo[2,3-d]pyrimidine Thienoyl Regioisomers as Targeted Antifolates for Folate Receptor alpha and the Proton-Coupled Folate Transporter in Human Tumors.,Wang L, Wallace A, Raghavan S, Deis SM, Wilson MR, Yang S, Polin L, White K, Kushner J, Orr S, George C, O'Connor C, Hou Z, Mitchell-Ryan S, Dann CE 3rd, Matherly LH, Gangjee A J Med Chem. 2015 Sep 10;58(17):6938-59. doi: 10.1021/acs.jmedchem.5b00801. Epub, 2015 Aug 28. PMID:26317331<ref>PMID:26317331</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4zz1" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Dann III CE]]
[[Category: Deis SM]]