View source for 7a13


==CRYSTAL STRUCTURE OF HUMAN METHIONINE AMINOPEPTIDASE-2 IN COMPLEX WITH AN INHIBITOR GSK1978537A (COMPOUND 27)==
<StructureSection load='7a13' size='340' side='right'caption='[[7a13]], [[Resolution|resolution]] 2.04&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A13 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A13 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]] 2.04&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=QW5:5-chloranyl-3-(3-methoxyphenyl)-1~{H}-indole-2-carboxamide'>QW5</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=7a13 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a13 OCA], [https://pdbe.org/7a13 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a13 RCSB], [https://www.ebi.ac.uk/pdbsum/7a13 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a13 ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Structure-based led optimisation of orally active reversible Methionine Aminopeptidase-2 (MetAP-2) inhibitors utilising a 'molecular budget' medicinal chemistry strategy is described. The key physicochemical parameters of target molecules (cLogP, molecular size and H-bond donor count) were monitored through straightforward and intuitive use of atom count and distribution. The balance between structure-based design and an awareness of the physico-chemical properties of the compounds synthesised enabled the rapid identification of a potent molecule with good oral pharmacokinetic (PK) characteristics by making fewer, higher quality compounds. The resulting candidate quality molecule was validated in a mechanistic cellular assay and a rodent secondary immunisation model.

Structure-based optimisation of orally active &amp; reversible MetAP-2 inhibitors maintaining a tight 'molecular budget'.,Hirst DJ, Brandt M, Bruton G, Christodoulou E, Cutler L, Deeks N, Goodacre JD, Jack T, Lindon M, Miah A, Page K, Parr N, Shukla L, Sims M, Thomas P, Thorpe J, Holmes DS Bioorg Med Chem Lett. 2020 Sep 9:127533. doi: 10.1016/j.bmcl.2020.127533. PMID:32919012<ref>PMID:32919012</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7a13" style="background-color:#fffaf0;"></div>

==See Also==
*[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Thorpe JH]]