Reversible binding of zinc in Plasmodium falciparum Sir2: structure and activity of the apoenzyme.
Reversible zinc chelation via thiol groups of cysteines leading to modulation of activity in redox regulated proteins forms a basis for switching on-off of various biochemical processes. Silent information regulator 2 (Sir2), a NAD(+) dependent deacetylase, contains a non-catalytic zinc ion coordinated by thiol groups of cysteines. Using Plasmodium falciparum Sir2 (PfSir2), we have examined the effect of zinc removal on the structure and activity of this enzyme. Our studies show that the enzyme with high affinity for zinc exhibits partial collapse of structure upon removal of the metal ion. Zinc reconstitution of apo PfSir2 led to recovery of both structure and activity highlighting the reversibility of the process.
Chakrabarty
Subhra Prakash
SP
Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, India.
Balaram
Hemalatha
H
D000595:Amino Acid Sequence; D001051:Apoenzymes; D003545:Cysteine / Q000378:metabolism; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000378:metabolism*; D011485:Protein Binding; D017510:Protein Folding; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D037761:Sirtuins / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
D001051:Apoenzymes; D015800:Protozoan Proteins; D013438:Sulfhydryl Compounds; D037761:Sirtuins; D015032:Zinc; D003545:Cysteine