X-ray crystal structure of Mycobacterium tuberculosis haloalkane dehalogenase Rv2579.
Haloalkane dehalogenases are enzymes well known to be important in bioremediation; the organisms from which they are produced are able to clean up toxic organohalides from polluted environments. However, besides being found in such contaminated environments, these enzymes have also been found in root or tissue-colonizing bacterial species. The haloalkane dehalogenase Rv2579 from Mycobacterium tuberculosis H37Rv has been cloned, expressed, purified and its crystal structure determined at high resolution (1.2A). In addition, the crystal structure of the enzyme has been determined in complex with the product from the reaction with 1,3-dibromopropane, i.e. 1,3-propanediol and in complex with the classical substrate of haloalkane dehalogenases, 1,2-dichloroethane. The enzyme is a two-domain protein having a catalytic domain of an alpha/beta hydrolase fold and a cap domain. The active site residues and the halide-stabilizing residues have been identified as Asp109, Glu133, His273, Asn39 and Trp110. Its overall structure is similar to those of other known haloalkane dehalogenases. Its mechanism of action involves an SN2 nucleophilic displacement.
Mazumdar
Pooja A
PA
Group in Protein Structure and Function, Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7.
Hulecki
Jordan C
JC
Cherney
Maia M
MM
Garen
Craig R
CR
James
Michael N G
MN
D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D005025:Ethylene Dichlorides / Q000737:chemistry / Q000378:metabolism; D019855:Ethylene Glycol / Q000737:chemistry / Q000378:metabolism; D006867:Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000235:genetics; D011409:Propylene Glycols / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein; D013379:Substrate Specificity; D014867:Water / Q000737:chemistry / Q000378:metabolism
D005025:Ethylene Dichlorides; D011409:Propylene Glycols; D014867:Water; C024565:ethylene dichloride; C041787:1,3-propanediol; D006867:Hydrolases; C046137:haloalkane dehalogenase; D019855:Ethylene Glycol