PDBsum entry 2b3h

Hydrolase

PDB id

2b3h

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Contents

			Protein chain

					304 a.a. *

			Ligands

					GOL ×2

			Metals

					_CO ×4


					__K


					_CL

			Waters ×511

* Residue conservation analysis

PDB id:

2b3h

Links

Name:

Hydrolase

Title:

Crystal structure of human methionine aminopeptidase type i with a third cobalt in the active site

Structure:

Methionine aminopeptidase 1. Chain: a. Fragment: residues 81-384. Synonym: metap 1, map 1, peptidase m 1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: metap1, kiaa0094. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.10Å

R-factor:

0.101

R-free:

0.131

Authors:

A.Addlagatta,X.Hu,J.O.Liu,B.W.Matthews

Key ref:

A.Addlagatta et al. (2005). Structural basis for the functional differences between type I and type II human methionine aminopeptidases. Biochemistry, 44, 14741-14749. PubMed id: 16274222 DOI: 10.1021/bi051691k

Date:

20-Sep-05

Release date:

22-Nov-05

PROCHECK

	Headers

	References

Protein chain

P53582 (MAP11_HUMAN) - Methionine aminopeptidase 1 from Homo sapiens

Seq: Struc:					386 a.a. 304 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.3.4.11.18 - methionyl aminopeptidase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

Release of N-terminal amino acids, preferentially methionine, from peptides and arylamides.

Cofactor:

Cobalt cation

DOI no: 10.1021/bi051691k	Biochemistry 44:14741-14749 (2005)
PubMed id: 16274222

Structural basis for the functional differences between type I and type II human methionine aminopeptidases.
A.Addlagatta, X.Hu, J.O.Liu, B.W.Matthews.

ABSTRACT

Determination of the crystal structure of human MetAP1 makes it possible, for the first time, to compare the structures of a Type I and a Type II methionine aminopeptidase (MetAP) from the same organism. Comparison of the Type I enzyme with the previously reported complex of ovalicin with Type II MetAP shows that the active site of the former is reduced in size and would incur steric clashes with the bound inhibitor. This explains why ovalicin and related anti-angiogenesis inhibitors target Type II human MetAP but not Type I. The differences in both size and shape of the active sites between MetAP1 and MetAP2 also help to explain their different substrate specificity. In the presence of excess Co(2+), a third cobalt ion binds in the active site region, explaining why metal ions in excess can be inhibitory. Also, the N-terminal region of the protein contains three distinct Pro-x-x-Pro motifs, supporting the prior suggestion that this region of the protein may participate in binding to the ribosome.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21246731

N.Mischerikow, and A.J.Heck (2011).
Targeted large-scale analysis of protein acetylation.

Proteomics, 11, 571-589.

20142044

O.Olaleye, T.R.Raghunand, S.Bhat, J.He, S.Tyagi, G.Lamichhane, P.Gu, J.Zhou, Y.Zhang, J.Grosset, W.R.Bishai, and J.O.Liu (2010).
Methionine aminopeptidases from Mycobacterium tuberculosis as novel antimycobacterial targets.

Chem Biol, 17, 86-97.

19660503

J.J.Alvarado, A.Nemkal, J.M.Sauder, M.Russell, D.E.Akiyoshi, W.Shi, S.C.Almo, and L.M.Weiss (2009).
Structure of a microsporidian methionine aminopeptidase type 2 complexed with fumagillin and TNP-470.

Mol Biochem Parasitol, 168, 158-167.

PDB codes:

3fm3 3fmq 3fmr

18952013

S.Mitra, B.Bennett, and R.C.Holz (2009).
Mutation of H63 and its catalytic affect on the methionine aminopeptidase from Escherichia coli.

Biochim Biophys Acta, 1794, 137-143.

19198897

S.Mitra, G.Sheppard, J.Wang, B.Bennett, and R.C.Holz (2009).
Analyzing the binding of Co(II)-specific inhibitors to the methionyl aminopeptidases from Escherichia coli and Pyrococcus furiosus.

J Biol Inorg Chem, 14, 573-585.

18343108

M.K.Haldar, M.D.Scott, N.Sule, D.K.Srivastava, and S.Mallik (2008).
Synthesis of barbiturate-based methionine aminopeptidase-1 inhibitors.

Bioorg Med Chem Lett, 18, 2373-2376.

18855426

S.J.Watterson, S.Mitra, S.I.Swierczek, B.Bennett, and R.C.Holz (2008).
Kinetic and spectroscopic analysis of the catalytic role of H79 in the methionine aminopeptidase from Escherichia coli.

Biochemistry, 47, 11885-11893.

19019076

S.Mitra, K.M.Job, L.Meng, B.Bennett, and R.C.Holz (2008).
Analyzing the catalytic role of Asp97 in the methionine aminopeptidase from Escherichia coli.

FEBS J, 275, 6248-6259.

17623657

P.Pullikotil, S.Benjannet, J.Mayne, and N.G.Seidah (2007).
The proprotein convertase SKI-1/S1P: alternate translation and subcellular localization.

J Biol Chem, 282, 27402-27413.

17656313

X.Hu, Y.Dang, K.Tenney, P.Crews, C.W.Tsai, K.M.Sixt, P.A.Cole, and J.O.Liu (2007).
Regulation of c-Src nonreceptor tyrosine kinase activity by bengamide A through inhibition of methionine aminopeptidases.

Chem Biol, 14, 764-774.

18093325

Z.Q.Ma, S.X.Xie, Q.Q.Huang, F.J.Nan, T.D.Hurley, and Q.Z.Ye (2007).
Structural analysis of inhibition of E. coli methionine aminopeptidase: implication of loop adaptability in selective inhibition of bacterial enzymes.

BMC Struct Biol, 7, 84.

PDB codes:

2q92 2q93 2q94 2q95 2q96

16823043

A.Addlagatta, and B.W.Matthews (2006).
Structure of the angiogenesis inhibitor ovalicin bound to its noncognate target, human Type 1 methionine aminopeptidase.

Protein Sci, 15, 1842-1848.

PDB code:

2gz5

16724298

X.Hu, A.Addlagatta, B.W.Matthews, and J.O.Liu (2006).
Identification of pyridinylpyrimidines as inhibitors of human methionine aminopeptidases.

Angew Chem Int Ed Engl, 45, 3772-3775.

PDB code:

2g6p

17114291

X.Hu, A.Addlagatta, J.Lu, B.W.Matthews, and J.O.Liu (2006).
Elucidation of the function of type 1 human methionine aminopeptidase during cell cycle progression.

Proc Natl Acad Sci U S A, 103, 18148-18153.

PDB codes:

2nq6 2nq7

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.