PDBsum entry 5ypd

Hydrolase

PDB id: 5ypd

Contents

Protein chain

282 a.a.

Ligands

MET

GOL ×2

Metals

_CO ×2

_NA

_CL

Waters ×162

PDB id:

5ypd

Name:

Hydrolase

Title:

Mycobacterium tuberculosis methionine aminopeptidase type 1c (c105n mutant) in complex with methionine

Structure:

Methionine aminopeptidase. Chain: a. Synonym: metap,peptidase m. Engineered: yes. Mutation: yes

Source:

Mycobacterium tuberculosis (strain atcc 25177 / h37ra). Organism_taxid: 419947. Strain: atcc 25177 / h37ra. Gene: mapb, map, mra_2886. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.62Å R-factor: 0.146 R-free: 0.182

Authors:

C.B.Sandeep,A.Addlagatta

Key ref:

S.C.Bala et al. (2019). Discovery of a new class of type 1 methionine aminopeptidases that have relaxed substrate specificity. Int J Biol Macromol, 129, 523-529. PubMed id: 30763644 DOI: 10.1016/j.ijbiomac.2019.02.055

Date:

01-Nov-17 Release date: 07-Nov-18

Protein chain

A5U6L5  (A5U6L5_MYCTA) -  Methionine aminopeptidase from Mycobacterium tuberculosis (strain ATCC 25177 / H37Ra)

Seq: 285 a.a.

Struc: 282 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.4.11.18 - methionyl aminopeptidase.
• Reaction: Release of N-terminal amino acids, preferentially methionine, from peptides and arylamides.
• Cofactor: Cobalt cation

DOI no: 10.1016/j.ijbiomac.2019.02.055

Int J Biol Macromol 129:523-529 (2019)

PubMed id: 30763644

Discovery of a new class of type 1 methionine aminopeptidases that have relaxed substrate specificity.

S.C.Bala, N.Haque, V.Pillalamarri, R.Reddi, R.Kashyap, A.K.Marapaka, A.Addlagatta.

ABSTRACT

Methionine aminopeptidases (MetAPs) are a class of enzymes evolved to cleave initiator methionine in 60-70% of the total cellular proteins in all living cells. Based on their sequence differences, they are classified into Type 1 and Type 2. Type 1 is further divided into Type 1a, 1a', 1b, 1c and 1d. Irrespective of various classifications, all MetAPs reported till date displayed hydrolytic activity against peptides that contain only methionine on the N-terminus. A cysteine at the top of the active site in all the Type 1 structures is reported to be critical for the specificity. Mutation of this cysteine to serine or asparagine leads to loss of specificity. In the present study, we have identified a class of MetAPs in some of the proteobacteria that have an asparagine at this site. Most of the proteobacteria that contain MetAP1n are pathogenic in nature. Biochemical and structural studies on two proteins, one from each of V. coralliilyticus and K. pneumoniae confirm that these enzymes cleave leucine in addition to methionine. Crystallographic and homology modeling studies suggest that relaxed substrate specificity of this new class of enzymes could be due to the increased flexibility in the active site. Since this new class has an asparagine at the critical position that probably contributes for the relaxed substrate specificity and also differentiates them from other Type 1 MetAPs, we classified them as Type 1n.