3CH3

Crystal Structure Analysis of SERA5E from plasmodium falciparum

Summary for 3CH3

• Entry DOI: 10.2210/pdb3ch3/pdb
• Related: 3CH2
• Descriptor: Serine-repeat antigen protein, POTASSIUM ION, DIHYDROGENPHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: cysteine protease, papain family, glycoprotein, hydrolase, malaria, thiol protease, vacuole
• Biological source: Plasmodium falciparum
• Cellular location: Parasitophorous vacuole : Q9TY95
• Total number of polymer chains: 1
• Total formula weight: 30897.32

Authors

Smith, B.J.,Malby, R.L.,Colman, P.M.,Clarke, O.B. (deposition date: 2008-03-07, release date: 2008-03-25, Last modification date: 2024-10-30)

Primary citation

Hodder, A.N.,Malby, R.L.,Clarke, O.B.,Fairlie, W.D.,Colman, P.M.,Crabb, B.S.,Smith, B.J.
Structural Insights into the Protease-like Antigen Plasmodium falciparum SERA5 and Its Noncanonical Active-Site Serine
J.Mol.Biol., 392:154-165, 2009

PubMed Abstract: The sera genes of the malaria-causing parasite Plasmodium encode a family of unique proteins that are maximally expressed at the time of egress of parasites from infected red blood cells. These multi-domain proteins are unique, containing a central papain-like cysteine-protease fragment enclosed between the disulfide-linked N- and C-terminal domains. However, the central fragment of several members of this family, including serine repeat antigen 5 (SERA5), contains a serine (S596) in place of the active-site cysteine. Here we report the crystal structure of the central protease-like domain of Plasmodium falciparum SERA5, revealing a number of anomalies in addition to the putative nucleophilic serine: (1) the structure of the putative active site is not conducive to binding substrate in the canonical cysteine-protease manner; (2) the side chain of D594 restricts access of substrate to the putative active site; and (3) the S(2) specificity pocket is occupied by the side chain of Y735, reducing this site to a small depression on the protein surface. Attempts to determine the structure in complex with known inhibitors were not successful. Thus, despite having revealed its structure, the function of the catalytic domain of SERA5 remains an enigma.

PubMed: 19591843
DOI: 10.1016/j.jmb.2009.07.007

Experimental method

X-RAY DIFFRACTION (1.79 Å)