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1yw8

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Revision as of 06:21, 25 April 2018

h-MetAP2 complexed with A751277

Structural highlights

1yw8 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:	1yw7, 1yw9
Gene:	METAP2, MNPEP, P67EIF2 (HUMAN)
Activity:	Methionyl aminopeptidase, with EC number 3.4.11.18
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MAP2_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). The catalytic activity of human METAP2 toward Met-Val peptides is consistently two orders of magnitude higher than that of METAP1, suggesting that it is responsible for processing proteins containing N-terminal Met-Val and Met-Thr sequences in vivo. Protects eukaryotic initiation factor EIF2S1 from translation-inhibiting phosphorylation by inhibitory kinases such as EIF2AK2/PKR and EIF2AK1/HCR. Plays a critical role in the regulation of protein synthesis.

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

Methionine aminopeptidase-2 (MetAP2) is a novel target for cancer therapy. As part of an effort to discover orally active reversible inhibitors of MetAP2, a series of anthranilic acid sulfonamides with micromolar affinities for human MetAP2 were identified using affinity selection by mass spectrometry (ASMS) screening. These micromolar hits were rapidly improved to nanomolar leads on the basis of insights from protein crystallography; however, the compounds displayed extensive binding to human serum albumin and had limited activity in cellular assays. Modifications based on structural information on the binding of lead compounds to both MetAP2 and domain III of albumin allowed the identification of compounds with significant improvements in both parameters, which showed good cellular activity in both proliferation and methionine processing assays.

Discovery and optimization of anthranilic acid sulfonamides as inhibitors of methionine aminopeptidase-2: a structural basis for the reduction of albumin binding.,Sheppard GS, Wang J, Kawai M, Fidanze SD, BaMaung NY, Erickson SA, Barnes DM, Tedrow JS, Kolaczkowski L, Vasudevan A, Park DC, Wang GT, Sanders WJ, Mantei RA, Palazzo F, Tucker-Garcia L, Lou P, Zhang Q, Park CH, Kim KH, Petros A, Olejniczak E, Nettesheim D, Hajduk P, Henkin J, Lesniewski R, Davidsen SK, Bell RL J Med Chem. 2006 Jun 29;49(13):3832-49. PMID:16789740^[1]

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

References

↑ Sheppard GS, Wang J, Kawai M, Fidanze SD, BaMaung NY, Erickson SA, Barnes DM, Tedrow JS, Kolaczkowski L, Vasudevan A, Park DC, Wang GT, Sanders WJ, Mantei RA, Palazzo F, Tucker-Garcia L, Lou P, Zhang Q, Park CH, Kim KH, Petros A, Olejniczak E, Nettesheim D, Hajduk P, Henkin J, Lesniewski R, Davidsen SK, Bell RL. Discovery and optimization of anthranilic acid sulfonamides as inhibitors of methionine aminopeptidase-2: a structural basis for the reduction of albumin binding. J Med Chem. 2006 Jun 29;49(13):3832-49. PMID:16789740 doi:10.1021/jm0601001

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1yw8"

Categories: Human | Methionyl aminopeptidase | Park, C H | Hydrolase

@@ Line 1: / Line 1: @@
 ==h-MetAP2 complexed with A751277==
 <StructureSection load='1yw8' size='340' side='right' caption='[[1yw8]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">METAP2, MNPEP, P67EIF2 ([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/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=1yw8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yw8 OCA], [http://pdbe.org/1yw8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1yw8 RCSB], [http://www.ebi.ac.uk/pdbsum/1yw8 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=1yw8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yw8 OCA], [http://pdbe.org/1yw8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1yw8 RCSB], [http://www.ebi.ac.uk/pdbsum/1yw8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1yw8 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/yw/1yw8_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/yw/1yw8_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1yw8

From Proteopedia

Revision as of 06:21, 25 April 2018

h-MetAP2 complexed with A751277

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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