PDBsum entry 2ckd

Transferase

PDB id: 2ckd

Contents

Protein chains

303 a.a. *

* Residue conservation analysis

PDB id:

2ckd

Name:

Transferase

Title:

Crystal structure of ml2640 from mycobacterium leprae

Structure:

Putative s-adenosyl-l-methionine-dependent methyltransferase ml2640. Chain: a, b. Synonym: hypothetical protein ml2640. Engineered: yes

Source:

Mycobacterium leprae. Organism_taxid: 1769. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Resolution:

2.80Å R-factor: 0.202 R-free: 0.255

Authors:

M.Grana,A.Buschiazzo,A.Wehenkel,A.Haouz,P.M.Alzari

Key ref:

M.Graña et al. (2007). The crystal structure of M. leprae ML2640c defines a large family of putative S-adenosylmethionine-dependent methyltransferases in mycobacteria. Protein Sci, 16, 1896-1904. PubMed id: 17660248 DOI: 10.1110/ps.072982707

Date:

17-Apr-06 Release date: 29-May-07

Protein chains

Q9CCZ4  (Y2640_MYCLE) -  Putative S-adenosyl-L-methionine-dependent methyltransferase ML2640 from Mycobacterium leprae (strain TN)

Seq: 310 a.a.

Struc: 303 a.a.

Enzyme reactions

• Enzyme class: E.C.2.1.1.- - ?????

DOI no: 10.1110/ps.072982707

Protein Sci 16:1896-1904 (2007)

PubMed id: 17660248

The crystal structure of M. leprae ML2640c defines a large family of putative S-adenosylmethionine-dependent methyltransferases in mycobacteria.

M.Graña, A.Haouz, A.Buschiazzo, I.Miras, A.Wehenkel, V.Bondet, W.Shepard, F.Schaeffer, S.T.Cole, P.M.Alzari.

ABSTRACT

Mycobacterium leprae protein ML2640c belongs to a large family of conserved hypothetical proteins predominantly found in mycobacteria, some of them predicted as putative S-adenosylmethionine (AdoMet)-dependent methyltransferases (MTase). As part of a Structural Genomics initiative on conserved hypothetical proteins in pathogenic mycobacteria, we have determined the structure of ML2640c in two distinct crystal forms. As expected, ML2640c has a typical MTase core domain and binds the methyl donor substrate AdoMet in a manner consistent with other known members of this structural family. The putative acceptor substrate-binding site of ML2640c is a large internal cavity, mostly lined by aromatic and aliphatic side-chain residues, suggesting that a lipid-like molecule might be targeted for catalysis. A flap segment (residues 222-256), which isolates the binding site from the bulk solvent and is highly mobile in the crystal structures, could serve as a gateway to allow substrate entry and product release. The multiple sequence alignment of ML2640c-like proteins revealed that the central alpha/beta core and the AdoMet-binding site are very well conserved within the family. However, the amino acid positions defining the binding site for the acceptor substrate display a higher variability, suggestive of distinct acceptor substrate specificities. The ML2640c crystal structures offer the first structural glimpses at this important family of mycobacterial proteins and lend strong support to their functional assignment as AdoMet-dependent methyltransferases.

Selected figure(s)

Figure 2.
Figure 2. (A) Structural superposition (RMSD 2.1 Å for 221 aligned residues) of the protein backbones of ML2640c (light brown) and

Figure 3.
Figure 3. (A) Residue conservation from the multiple alignment of ML2640c-like sequences (Supplemental Fig. 1) mapped onto the

The above figures are reprinted by permission from the Protein Society: Protein Sci (2007, 16, 1896-1904) copyright 2007.

Figures were selected by the author.