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4u6e

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Revision as of 01:25, 19 January 2017

HsMetAP in complex with (amino(phenyl)methyl)phosphonic acid

Structural highlights

4u6e is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4u1b, 4u69, 4u6c, 4u6j, 4u6w, 4u6z, 4u70, 4u71, 4u73, 4u75, 4u76
Activity:	Methionyl aminopeptidase, with EC number 3.4.11.18
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MAP11_HUMAN] Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). Required for normal progression through the cell cycle.[HAMAP-Rule:MF_03174]^[1] ^[2]

Publication Abstract from PubMed

The methionine aminopeptidase (MetAP) family is responsible for the cleavage of the initiator methionine from newly synthesized proteins. Currently, there are no small molecule inhibitors that show selectivity toward the bacterial MetAPs compared to the human enzyme. In our current study, we have screened 20 alpha-aminophosphonate derivatives and identified a molecule (compound 15) that selectively inhibits the S. pneumonia MetAP in low micromolar range but not the human enzyme. Further bioinformatics, biochemical, and structural analyses suggested that phenylalanine (F309) in the human enzyme and methionine (M205) in the S. pneumonia MetAP at the analogous position render them with different susceptibilities against the identified inhibitor. X-ray crystal structures of various inhibitors in complex with wild type and F309M enzyme further established the molecular basis for the inhibitor selectivity.

Identification of the Molecular Basis of Inhibitor Selectivity between the Human and Streptococcal Type I Methionine Aminopeptidases.,Arya T, Reddi R, Kishor C, Ganji RJ, Bhukya S, Gumpena R, McGowan S, Drag M, Addlagatta A J Med Chem. 2015 Mar 12;58(5):2350-7. doi: 10.1021/jm501790e. Epub 2015 Feb 27. PMID:25699713^[3]

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

References

↑ Addlagatta A, Hu X, Liu JO, Matthews BW. Structural basis for the functional differences between type I and type II human methionine aminopeptidases. Biochemistry. 2005 Nov 15;44(45):14741-9. PMID:16274222 doi:10.1021/bi051691k
↑ Hu X, Addlagatta A, Lu J, Matthews BW, Liu JO. Elucidation of the function of type 1 human methionine aminopeptidase during cell cycle progression. Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18148-53. Epub 2006 Nov 17. PMID:17114291
↑ Arya T, Reddi R, Kishor C, Ganji RJ, Bhukya S, Gumpena R, McGowan S, Drag M, Addlagatta A. Identification of the Molecular Basis of Inhibitor Selectivity between the Human and Streptococcal Type I Methionine Aminopeptidases. J Med Chem. 2015 Mar 12;58(5):2350-7. doi: 10.1021/jm501790e. Epub 2015 Feb 27. PMID:25699713 doi:http://dx.doi.org/10.1021/jm501790e

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/4u6e"

@@ Line 1: / Line 1: @@
 ==HsMetAP in complex with (amino(phenyl)methyl)phosphonic acid==
 <StructureSection load='4u6e' size='340' side='right' caption='[[4u6e]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4u1b|4u1b]], [[4u69|4u69]], [[4u6c|4u6c]], [[4u6j|4u6j]], [[4u6w|4u6w]], [[4u6z|4u6z]], [[4u70|4u70]], [[4u71|4u71]], [[4u73|4u73]], [[4u75|4u75]], [[4u76|4u76]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methionyl_aminopeptidase Methionyl aminopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.11.18 3.4.11.18] </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=4u6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u6e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u6e RCSB], [http://www.ebi.ac.uk/pdbsum/4u6e 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=4u6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u6e OCA], [http://pdbe.org/4u6e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4u6e RCSB], [http://www.ebi.ac.uk/pdbsum/4u6e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4u6e ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4u6e" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4u6e

From Proteopedia

Revision as of 01:25, 19 January 2017

HsMetAP in complex with (amino(phenyl)methyl)phosphonic acid

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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