Streptococcus pneumonia is the common cause of sepsis and meningitis. Emergence of multiple antibiotic resistant strains in the community‐acquired bacterium is catastrophic. Glucose kinase (GLK) is a regulatory enzyme capable of adding phosphate group to glucose in the first step of streptomycin biosynthesis. The activity of glucose kinase was regulated by the Carbon Catabolite Repression (CCR) system. Therefore, it is important to establish the structure‐function relation of GLK in S. pneumoniae. However, a solved structure for S. pneumoniae GLK is not available at the protein data bank (PDB). Therefore, we created a model of GLK from S. pnemoniae using the X‐ray structure of Glk from E. faecalis as template with MODELLER (a comparative modeling program). The model was validated using protein structure checking tools such as PROCHECK, WHAT IF and ProSA for reliability. The active site amino acid Asp114 in the template is retained in S. pneumoniae GLK model (Asp115). Solvent accessible surface area (ASA) analysis of the GLK model showed that known key residues playing important role in active site for ligand binding and metal ion binding are buried and hence not accessible to solvent. The information thus discussed provides insight to the molecular understanding of glucose kinase in S. pneumoniae.

The continuing battles in the hospitals against drugresistant bacteria highlight the need for new antibiotics. The world largest causes of mortality and morbidity of pneumonia is caused by Streptococcus pneumoniae (S. pneumonia). S. pneumoniae is the most common cause of fatal community‐acquired pneumonia, middle ear infection and meningitis. The disease rate is especially high in young children, the elderly and immuno‐compromised individuals with predisposing conditions such as asplenia or acquired immunodeficiency syndrome (AIDS) [1, 2,3]. More than 90 different pneumococcal serotypes have been identified by their difference in polysaccharide capsules. However, about 90% of clinical episodes of invasive pneumococcal infections in humans are caused by 23 pneumococcal serotypes [4]. The mortality in the United Staes alone is about 40,000 per yea which is, higher than that for other bacterial diseases [5,6]. The efficacy of available vaccines is limited. The use of antibiotics results in either capsular type shifting or in the rapid appearance and spread of antibiotic resistance determinants [7,8, 9]. Thus prevention and treatment of the infection is a top priority for the scientific community [10]. This requires a better understanding of the S. pneumoniae proteins using structural and functional data for target definition and validation. Here, we describe the modeled structure of glucose kinase (GLK) from S. pneumonia towards establishing its molecular function. GLK (E.C.2.7.1.2) is an important enzyme in the biosynthesis of streptomycin. Glk catalyzes the conversion of glucose to glucose‐6‐phosphate and is catabolically repressed by higher concentrations of glucose (carbon catabolite repression (CCR)). However, a 3‐dimenisonal structure for S. pneumonia GLK is yet not available. Hence, we constructed the model structure for S. pneumonia GLK using known structural templates and describe its structural features to understand molecular function.

The structure of S. pneumoniae GLK is important for establishing its molecular function. However, a three dimensional structure is not available as yet at PDB. We developed a homology model for S. pneumoniae GLK using MODELLER. The model was further analyzed for residue solvent accessibility in establishing its molecular function. Solvent accessible surface area (ASA) analysis of the GLK model showed that known key residues playing important role in active site for ligand binding and metal ion binding are buried and not accessible to solvent. The analysis highlights the importance of solvent exposed catalytic residues in molecular function.