2adu

Structural highlights

Function

[AMPM2_HUMAN] Removes the N-terminal methionine from nascent proteins. 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.^{[1] [2] [3] [4]} 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.^{[5] [6] [7] [8]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Aminopeptidase 3D structures

References

1. ↑ Datta B, Ray MK, Chakrabarti D, Wylie DE, Gupta NK. Glycosylation of eukaryotic peptide chain initiation factor 2 (eIF-2)-associated 67-kDa polypeptide (p67) and its possible role in the inhibition of eIF-2 kinase-catalyzed phosphorylation of the eIF-2 alpha-subunit. J Biol Chem. 1989 Dec 5;264(34):20620-4. PMID:2511207
2. ↑ 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
3. ↑ Towbin H, Bair KW, DeCaprio JA, Eck MJ, Kim S, Kinder FR, Morollo A, Mueller DR, Schindler P, Song HK, van Oostrum J, Versace RW, Voshol H, Wood J, Zabludoff S, Phillips PE. Proteomics-based target identification: bengamides as a new class of methionine aminopeptidase inhibitors. J Biol Chem. 2003 Dec 26;278(52):52964-71. Epub 2003 Oct 8. PMID:14534293 doi:10.1074/jbc.M309039200
4. ↑ Marino JP Jr, Fisher PW, Hofmann GA, Kirkpatrick RB, Janson CA, Johnson RK, Ma C, Mattern M, Meek TD, Ryan MD, Schulz C, Smith WW, Tew DG, Tomazek TA Jr, Veber DF, Xiong WC, Yamamoto Y, Yamashita K, Yang G, Thompson SK. Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore. J Med Chem. 2007 Aug 9;50(16):3777-85. Epub 2007 Jul 18. PMID:17636946 doi:10.1021/jm061182w
5. ↑ Datta B, Ray MK, Chakrabarti D, Wylie DE, Gupta NK. Glycosylation of eukaryotic peptide chain initiation factor 2 (eIF-2)-associated 67-kDa polypeptide (p67) and its possible role in the inhibition of eIF-2 kinase-catalyzed phosphorylation of the eIF-2 alpha-subunit. J Biol Chem. 1989 Dec 5;264(34):20620-4. PMID:2511207
6. ↑ 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
7. ↑ Towbin H, Bair KW, DeCaprio JA, Eck MJ, Kim S, Kinder FR, Morollo A, Mueller DR, Schindler P, Song HK, van Oostrum J, Versace RW, Voshol H, Wood J, Zabludoff S, Phillips PE. Proteomics-based target identification: bengamides as a new class of methionine aminopeptidase inhibitors. J Biol Chem. 2003 Dec 26;278(52):52964-71. Epub 2003 Oct 8. PMID:14534293 doi:10.1074/jbc.M309039200
8. ↑ Marino JP Jr, Fisher PW, Hofmann GA, Kirkpatrick RB, Janson CA, Johnson RK, Ma C, Mattern M, Meek TD, Ryan MD, Schulz C, Smith WW, Tew DG, Tomazek TA Jr, Veber DF, Xiong WC, Yamamoto Y, Yamashita K, Yang G, Thompson SK. Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4-triazole pharmacophore. J Med Chem. 2007 Aug 9;50(16):3777-85. Epub 2007 Jul 18. PMID:17636946 doi:10.1021/jm061182w
9. ↑ Kallander LS, Lu Q, Chen W, Tomaszek T, Yang G, Tew D, Meek TD, Hofmann GA, Schulz-Pritchard CK, Smith WW, Janson CA, Ryan MD, Zhang GF, Johanson KO, Kirkpatrick RB, Ho TF, Fisher PW, Mattern MR, Johnson RK, Hansbury MJ, Winkler JD, Ward KW, Veber DF, Thompson SK. 4-Aryl-1,2,3-triazole: a novel template for a reversible methionine aminopeptidase 2 inhibitor, optimized to inhibit angiogenesis in vivo. J Med Chem. 2005 Sep 8;48(18):5644-7. PMID:16134930 doi:10.1021/jm050408c