Biochemistry - Publicatons

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Browsing Biochemistry - Publicatons by Author "Akhter, Yusuf"
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    Crystallization and preliminary X-ray crystallographic studies of Mycobacterium tuberculosis CRP/FNR family transcription regulator
    ( 2006-09-01) Akif, Mohd ; Akhter, Yusuf ; Hasnain, Seyed E. ; Mande, Shekhar C.
    CRP/FNR family members are transcription factors that regulate the transcription of many genes in Escherichia coli and other organisms. Mycobacterium tuberculosis H37Rv contains a probable CRP/FNR homologue encoded by the open reading frame Rv3676. The deletion of this gene is known to cause growth defects in cell culture, in bone marrow-derived macrophages and in a mouse model of tuberculosis. The mycobacterial gene Rv3676 shares ∼32% sequence identity with prototype E. coli CRP. The structure of the protein might provide insight into transcriptional regulation in the pathogen by this protein. The M. tuberculosis CRP/FNR transcription regulator was crystallized in space group P212121, with unit-cell parameters a = 54.1, b = 84.6, c = 101.2 Å. The crystal diffracted to a resolution of 2.9 Å. Matthews coefficient and self-rotation function calculations reveal the presence of two monomers in the asymmetric unit. © 2006 International Union of Crystallography All rights reserved.
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    Mapping conformational transitions in cyclic AMP receptor protein: Crystal structure and normal-mode analysis of mycobacterium tuberculosis apo-cAMP receptor protein
    ( 2010-01-20) Kumar, Pramod ; Joshi, Dhananjay C. ; Akif, Mohd ; Akhter, Yusuf ; Hasnain, Seyed E. ; Mande, Shekhar C.
    Cyclic AMP (cAMP) receptor protein, which acts as the sensor of cAMP levels in cells, is a well-studied transcription factor that is best known for allosteric changes effected by the binding of cAMP. Although genetic and biochemical data on the protein are available from several sources, structural information about the cAMP-free protein has been lacking. Therefore, the precise atomic events that take place upon binding of cAMP, leading to conformational changes in the protein and its activation to bind DNA, have been elusive. In this work we solved the cAMP-free crystal structure of the Mycobacterium tuberculosis homolog of cAMP receptor protein at 2.9 Å resolution, and carried out normal-mode analysis to map conformational transitions among its various conformational states. In our structure, the cAMP-binding domain holds onto the DNA-binding domain via strong hydrophobic interactions, thereby freezing the latter in a conformation that is not competent to bind DNA. The two domains release each other in the presence of cAMP, making the DNA-binding domain more flexible and allowing it to bind its cognate DNA via an induced-fit mechanism. The structure of the cAMP-free protein and results of the normalmode analysis therefore highlight an elegant mechanism of the allosteric changes effected by the binding of cAMP. © 2010 by the Biophysical Society.