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| | ==Mn Form Of E. coli Methionine Aminopeptidase In Complex With a quinolinyl sulfonamide inhibitor== | | ==Mn Form Of E. coli Methionine Aminopeptidase In Complex With a quinolinyl sulfonamide inhibitor== |
| - | <StructureSection load='2bb7' size='340' side='right' caption='[[2bb7]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='2bb7' size='340' side='right'caption='[[2bb7]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2bb7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BB7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BB7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2bb7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BB7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BB7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=QMS:N-(QUINOLIN-8-YL)METHANESULFONAMIDE'>QMS</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">map ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=QMS:N-(QUINOLIN-8-YL)METHANESULFONAMIDE'>QMS</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=2bb7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bb7 OCA], [https://pdbe.org/2bb7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bb7 RCSB], [https://www.ebi.ac.uk/pdbsum/2bb7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bb7 ProSAT]</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=2bb7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bb7 OCA], [http://pdbe.org/2bb7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bb7 RCSB], [http://www.ebi.ac.uk/pdbsum/2bb7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2bb7 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AMPM_ECOLI AMPM_ECOLI]] Removes the N-terminal methionine from nascent proteins. | + | [https://www.uniprot.org/uniprot/MAP1_ECOLI MAP1_ECOLI] 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). Requires deformylation of the N(alpha)-formylated initiator methionine before it can be hydrolyzed.[HAMAP-Rule:MF_01974]<ref>PMID:20521764</ref> <ref>PMID:3027045</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Aminopeptidase|Aminopeptidase]] | + | *[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus coli migula 1895]] | + | [[Category: Escherichia coli]] |
| - | [[Category: Methionyl aminopeptidase]] | + | [[Category: Large Structures]] |
| - | [[Category: Ye, Q Z]] | + | [[Category: Ye QZ]] |
| - | [[Category: Enzyme-inhibitor complex]]
| + | |
| - | [[Category: Hydrolase]]
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| - | [[Category: Metalloenzyme]]
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| - | [[Category: Trimetallic]]
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| Structural highlights
Function
MAP1_ECOLI 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). Requires deformylation of the N(alpha)-formylated initiator methionine before it can be hydrolyzed.[HAMAP-Rule:MF_01974][1] [2]
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
Quinolinyl sulfonamides, such as N-(quinolin-8-yl)methanesulfonamide (10) and N-(5-chloroquinolin-8-yl)methanesulfonamide (11), were identified as potent methionine aminopeptidase (MetAP) inhibitors by high throughput screening of a diverse chemical library of small organic compounds. They showed different inhibitory potencies on Co(II)-, Ni(II)-, Fe(II)-, Mn(II)-, and Zn(II)-forms of Escherichia coli MetAP, and their inhibition is dependent on metal concentration. X-ray structures of E. coli MetAP complexed with 10 revealed that the inhibitor forms a metal complex with the residue H79 at the enzyme active site; the complex is further stabilized by an extended H-bond and metal interaction network. Analysis of the inhibition of MetAP by these inhibitors indicates that this is a typical mechanism of inhibition for many non-peptidic MetAP inhibitors and emphasizes the importance of defining in vitro conditions for identifying and evaluating MetAP inhibitors that will be capable of giving information relevant to the in vivo situation.
Metal mediated inhibition of methionine aminopeptidase by quinolinyl sulfonamides.,Huang M, Xie SX, Ma ZQ, Hanzlik RP, Ye QZ Biochem Biophys Res Commun. 2006 Jan 13;339(2):506-13. Epub 2005 Nov 15. PMID:16300729[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Xiao Q, Zhang F, Nacev BA, Liu JO, Pei D. Protein N-terminal processing: substrate specificity of Escherichia coli and human methionine aminopeptidases. Biochemistry. 2010 Jul 6;49(26):5588-99. doi: 10.1021/bi1005464. PMID:20521764 doi:http://dx.doi.org/10.1021/bi1005464
- ↑ Ben-Bassat A, Bauer K, Chang SY, Myambo K, Boosman A, Chang S. Processing of the initiation methionine from proteins: properties of the Escherichia coli methionine aminopeptidase and its gene structure. J Bacteriol. 1987 Feb;169(2):751-7. PMID:3027045
- ↑ Huang M, Xie SX, Ma ZQ, Hanzlik RP, Ye QZ. Metal mediated inhibition of methionine aminopeptidase by quinolinyl sulfonamides. Biochem Biophys Res Commun. 2006 Jan 13;339(2):506-13. Epub 2005 Nov 15. PMID:16300729 doi:10.1016/j.bbrc.2005.11.042
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