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Publication Abstract from PubMed

The crystal structure of the methionine aminopeptidase (MetAP) from Mycobacterium tuberculosis (MtMetAP1c) has been determined in the apo- and methionine-bound forms. This is the first structure of a type I MetAP with a significant extension at the amino terminus. The catalytic domain is similar to that of Escherichia coli MetAP (EcMetAP), and the additional 40-residue segment wraps around the surface with an extended but well-defined structure. There are several members of the actinomyces family of bacteria that contain MetAPs with such N-terminal extensions, and we classify these as MetAP type Ic (MetAP1c). Some members of this family of bacteria also contain a second MetAP (type Ia) similar in size to EcMetAP. The main difference between the apo- and the methionine-bound forms of MtMetAP1c is in the conformation of the metal-binding residues. The position of the methionine bound in the active site is very similar to that found in many of the known members of this family. Side chains of several residues in the S1 and S1' subsites shift as much as 1.5 A compared to EcMetAP. Residues 14-17 have the sequence Pro-Thr-Arg-Pro and adopt the conformation of a polyproline II helix. Model-building suggests that this PxxP segment can bind to an SH3 protein motif. Other type Ib and type Ic MetAPs with N-terminal extensions contain similarly located PxxP motifs. Also, several ribosomal proteins are known to include SH3 domains, one of which is located close to the tunnel from which the nascent polypeptide chain exits the ribosome. Therefore, it is proposed that the binding of MetAPs to the ribosome is mediated by a complex between a PxxP motif on the protein and an SH3 domain on the ribosome. It is also possible that zinc-finger domains, which are located at the extreme N-terminus of type I MetAPs, may participate in interactions with the ribosome.

Identification of an SH3-binding motif in a new class of methionine aminopeptidases from Mycobacterium tuberculosis suggests a mode of interaction with the ribosome.,Addlagatta A, Quillin ML, Omotoso O, Liu JO, Matthews BW Biochemistry. 2005 May 17;44(19):7166-74. PMID:15882055^[3]

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