4km3

From Proteopedia

Discovery of a novel structural motif in methionine aminopeptidase from Streptococci with possible post-translational modification

Structural highlights

4km3 is a 2 chain structure with sequence from Streptococcus pneumoniae CGSP14. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.2Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

B2IQ22_STRPS 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 (By similarity).[HAMAP-Rule:MF_01974]

Publication Abstract from PubMed

Protein N-terminal methionine excision is an essential co-translational process that occurs in the cytoplasm of all organisms. About 60-70% of the newly synthesized proteins undergo this modification. Enzyme responsible for the removal of initiator methionine is methionine aminopeptidase (MetAP), which is a dinuclear metalloprotease. This protein is conserved through all forms of life from bacteria to human except viruses. MetAP is classified into two isoforms, Type I and II. Removal of the map gene or chemical inhibition is lethal to bacteria and to human cell lines, suggesting that MetAP could be a good drug target. In the present study we describe the discovery of a new genetic variant of the Type I MetAP that is present predominantly in the streptococci bacteria. There are two inserts (insert one: 27 amino acids and insert two: four residues) within the catalytic domain. Possible glycosylation and phosphorylation posttranslational modification sites are identified in the 'insert one'. Biochemical characterization suggests that this enzyme behaves similar to other MetAPs in terms of substrate specificity. Crystal structure Type Ia MetAP from Streptococcus pneumoniae (SpMetAP1a) revealed that it contains two molecules in the asymmetric unit and well ordered inserts with structural features that corroborate the possible posttranslational modification. Both the new inserts found in the SpMetAP1a structurally align with the P-X-X-P motif found in the M. tuberculosis and human Type I MetAPs as well as the 60 amino acid insert in the human Type II enzyme suggesting possible common function. In addition, one of the beta-hairpins within in the catalytic domain undergoes a flip placing a residue which is essential for enzyme activity away from the active site and the beta-hairpin loop of this secondary structure in the active site obstructing substrate binding. This is the first example of a MetAP crystallizing in the inactive form.

Discovery of a new genetic variant of methionine aminopeptidase from Streptococci with possible post-translational modifications: biochemical and structural characterization.,Arya T, Kishor C, Saddanapu V, Reddi R, Addlagatta A PLoS One. 2013 Oct 4;8(10):e75207. doi: 10.1371/journal.pone.0075207. PMID:24124477^[1]

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

References

↑ Arya T, Kishor C, Saddanapu V, Reddi R, Addlagatta A. Discovery of a new genetic variant of methionine aminopeptidase from Streptococci with possible post-translational modifications: biochemical and structural characterization. PLoS One. 2013 Oct 4;8(10):e75207. doi: 10.1371/journal.pone.0075207. PMID:24124477 doi:http://dx.doi.org/10.1371/journal.pone.0075207