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The University of Southampton
Biological Sciences
Email:
M.Akhtar@soton.ac.uk

Professor Muhammad Akhtar FRS

Emeritus Professor

Professor Muhammad Akhtar's photo

Professor Muhammad Akhtar is Emeritus Professor within Biological Sciences at the University of Southampton.

Career history

2004-Present: Distinguished National Professor, Higher Education Commission, Islamabad, Pakistan.
2002-Present: Director General, School of Biological Sciences, University of the Punjab, Pakistan.
1998-Present: Emeritus Professor of Biochemistry, University of Southampton, UK.
1990-1994: Director, SERC Molecular Recognition Centre, UK.
1989-1990: Chairman, Institute of Biomolecular Sciences, UK.
1983-1987: Chairman, School of Biochemical & Physiological Sciences, UK.
1978-1993: Head of Department of Biochemistry, University of Southampton, UK.
1973-1998: Professor of Biochemistry, University of Southampton, UK.
1968-1973: Reader, University of Southampton, UK.
1966-1968: Senior Lecturer, University of Southampton, UK.
1963-1966: Lecturer, University of Southampton, UK.
1963-1966: Department of Biochemistry, University of Southampton, UK.
1959-1963: Research Scientist, Research Institute, Cambridge, MA, USA.

Academic qualifications

1959: PhD, DIC Imperial College, University of London, UK.
1954: MSc (Gold Medallist) University of Punjab, Pakistan.
1952: BSc Government College, University of Punjab at Lahore, Pakistan.

Research

Publications

Contributions

Contact

Research interests

My research has been concerned with the elucidation of the stereochemistry and chemical mechanisms of enzymes involved in the biosynthesis of complex natural products and studies on visual proteins.  I have been at the forefront of applying the principles of stereochemistry and mechanistic organic chemistry to the elucidation of a wide variety of biological problems.  The strategy initiated by me nearly a quarter of a century ago has culminated in the delineation of the basic molecular mechanisms through which biological systems may carry out complex chemical transformations.  I have contributed to the understanding of the mechanisms through which the intricate architectures of cholesterol and ergosterol are elaborated by mammalian liver and yeast respectively [1,2], haem which is one of the components of the oxygen carrying protein, haemoglobin, is produced in the red blood cells [3] and sex hormones, androgen and oestrogen are biosynthesised in gonads [4, 5].  Apart from their relevance to biosyntheses, cumulatively these studies defined the complete substrate stereochemistry of at least a dozen enzymes and also shed new light on their catalytic mechanisms.  In many instances the mechanistic principles signalled by these investigations were found to typify a general phenomenon.

My work, carried out in collaboration with Neville Wright, on oestrogen biosynthesis was seminal in highlighting that certain P-450 group of enzymes catalyse a diverse range of generic reactions at a single active site [4].  This discovery prompted a critical analysis of the chemical features of iron-containing-oxygen-binding proteins and led to the proposal of a unified hypothesis which views a wide variety of biological oxidation processes as variations on a common mechanistic theme [6].  The insight provided by such studies is helping in designing a novel class of antioestrogens which have potential use in the treatment of one particular type of breast cancer [5]. 

Another area of research pursued in my laboratory used modern techniques of recombinant DNA technology and was directed to unearth the mechanisms underlying the production of antibiotics by microorganism and also the origin of antibiotic resistance in clinical isolates [7].

My longstanding interest in the vision field which is distinguished by studies on the elucidation of the mode and site of binding of the retinal chromophore in bovine rhodopsin [8, 9] has found general application to other classes of retinal-based proteins.[10]  Now the primary sequences of a large number of visual proteins including four from human eye have been elucidated by other workers using either protein or DNA sequencing.  In all these cases the site of retinal-binding was inferred from my original experimental work on bovine rhodopsin.  My group was also the first to describe the structure of bovine rhodopsin in terms of seven trans-membrane segments [11].  This latter feature which was subsequently confirmed in other laboratories using more advanced approaches seems to have been conserved in the structures of all animal rhodopsins described to date.  In subsequent years my research in the field moved towards the exciting goal of understanding the molecular mechanisms through which rhodopsin  after being activated by light interacts with other proteins of the retina setting the stage first for the transmission of message to brain and then termination of the signal in preparation for the next event.  The latter scenario is accomplished by two enzymes, rhodopsin kinase, which was discovered by others and phosphoopsin phosphates described by  my group [12, 13].  Furthermore, my group has shed new light on the mechanism action of rhodopsin kinase [14].

After my retirement from Southampton University in 1998, I retained a small research group until 2002 working predominantly on CYP17, an enzyme involved in androgen as well as corticoid biosynthesis, in collaboration with my wife, Monika Akhtar, a postdoctoral colleague, Peter Lee-Robichaud, and Neville Wright [5].  We made, what I believe to be an important discovery, that the CYP17's side-chain cleavage activity, required for androgen production in the testes but suppressed in the adrenal is dependent on the regulation of the enzyme by cytochrome b5 [5, 15].

In 2003 I was invited to Pakistan to set up a School of Biological Sciences for PhD training in biomedical sciences.  Apart from organizational and administrative duties I had to renew my hobby of supervision of PhD students.   Consequently, to sixty students, who did their PhD with me in Southampton seven more have been added in Lahore, with another six at various stages of preparation of their doctoral thesis.   Research-wise, apart from continuing mechanistic work on aminolevulinate synthase class of enzymes [16], I have set up a programme of research on the expression and purification of proteins of biomedical and industrial importance.   In a few cases proteins engineered in Lahore have been used for biophysical studies in Southampton by Neville Wright [17, 18], Jon Copper (now in UCL) [19] and Phil Williamson.  Our collaborative work with Neville has been particularly satisfying since this has enabled to us to use the H/D exchange approach, we had often talked of in the past, to successfully probe the interrelations between the secondary structure elements of insulin from various species to  their corresponding proinsulin [17, 18].

Research group

Molecular and Cellular Biosciences

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References: the order of the references is as cited in 'Research Interests'.

1. Substrate activation in pyridine nucleotide linked reactions: Illustrations from the steroid field.
M. Akhtar, D.C. Wilton, I.A. Watkinson and A.D. Rahimtula.
Proc. R. Soc. Lond. B 180, 167 177 (1972)

2. Some biological transformations involving unsaturated linkages: The importance of charge separation and charge neutralisation in enzyme catalysis.
M. Akhtar and C. Jones.
Tetrahedron Report 34, 1 20 (1978)

3. Mechanism and stereochemistry of enzymic reactions involved in porphyrin biosynthesis.
M. Akhtar, M.M. Abboud, G. Barnard, P. Jordan and Z. Zaman.
Phil. Trans. R. Soc. Lond. B. 273, 117 136 (1976)

 
4. Mechanistic studies on C 19 demethylation in oestrogen biosynthesis.
M. Akhtar, M.R. Calder, D.L. Corina and J.N. Wright.
Biochem. J. 201, 569 580 (1982)

5. A review of mechanistic studies on aromatase (CY19) and 17α-hydroxylase-17, 20-lyase (CY17)
 Muhammad Akhtar, J. Neville Wright, Peter Lee-Robichaud
 J. Steroid Biochem. and Mol. Biol. 125: 2-12 (2011).

6. A unified mechanistic view of oxidative reactions catalysed by P-450 and related Fe-containing enzymes.
M. Akhtar and J.N. Wright.
Natural Products Reports, 8, 527-612 (1991).

7. Sequence and interspecies transfer of an aminoglycoside phosphotransferase gene (APH) of Bacillus circulans.
C.J. Herbert, M. Sarwar, S.S. Ner, I.G. Giles and M. Akhtar.
Biochem.J. 233, 383 393 (1986).

8. Studies on vision: The nature of the retinal opsin linkage.
M. Akhtar, P.T. Blosse and P.B. Dewhurst.
Biochem. J. 110, 693 (1969)

9. Structural studies on membrane bound bovine rhodopsin.
E. Mullen and M. Akhtar.
Biochem. J. 211, 45 54 (1983)

10. The incorporation of tritiated retinyl moiety into the active site lysine residue of bacteriorhodopsin.
E. Mullen, M.G. Gore and M. Akhtar.
Biochem. J. 183, 175 178 (1979)

11. Topography of the rhodopsin molecule: Identification of the domain phosphorylated.
G.J. Sale, P. Towner and M. Akhtar.
Biochem. J. 175, 421 430 (1978)

12. Interplay of phosphorylation and dephosphorylation in vision: Protein phosphatases of bovine rod outer segments.
C. Fowles and M. Akhtar.
Biochemistry, 28, 9385 9391 (1989).

13. The phospho-opsin phosphatase from bovine rod outer segments: An insight into the mechanism of stimulation of type-2A protein phosphatase activity by protamine.  Alastair J. King, Natasa Andjelkovic, Brian A. Hemmings & Muhammad Akhtar. Eur.J.Biochem., 225, 383-394 (1994).

14. Mechanistic studies on rhodopsin kinase: Light-dependent phosphorylation of C-terminal peptides of rhodopsin.
Neil G. Brown, Charles Fowles, Ram Sharma and Muhammad Akhtar
Eur. J. Biochem. 208, 659-667 (1992).

15. Lysine mutagenesis identifies cationic charges of human CYP17 which interact with cytochrome b5 to promote male sex hormone biosynthesis.
P. Lee-Robichaud, M.E. Akhtar, M. Akhtar
Biochem. J. 342, 309-312 (1999)


16. Mechanism and substrate stereochemistry of 2-amino-3-oxobutyrate CoA ligase: implications for 5-aminolevulinate synthease and related enzymes
 Qamar Bashir, Naeem Rashid and Muhammad Akhtar
 Chem. Commun. 5065-5067 (2006).

17. Inventory of ‘slow exchanging' hydrogen atoms in human proinsulin and its derivatives: Observations on the mass spectrometric analysis of deuterio-proteins in D2O.
 Qurra-tul-Ann Afza Gardner, Hooria Younas, Naeem Rashid, J. Neville Wright, Muhammad Akhtar,
 Biochimica Biophysica Acta 1794 1224-1233 (2009).

18. Conformational transmission in proinsulin and its derivatives: A study using H/D exchange.
 Hooria Younas, Qurra-tul-Ann Afza Gardner, Naeem Rashid, J. Neville Wright, Muhammad Akhtar
 Int. J. of Mass Spectrom. 302 36-43 (2011).

19. Structure and Function of the L-threonine Dehydrogenase (Tk TDH) from the hyperthermophilic archaeon Thermococcus kodakaraensis
 A. Bowyer , H. Mikolajek , J.W. Stuart , S.P. Wood, F. Jamil , N. Rashid , M. Akhtar , J.B. Cooper.
 Journal of structural Biology  168: 294-304 (2009).

Professional responsibilities

  • 2010: Honorary Fellow University College, London, UK.
  • 2000: Foreign Fellow of Pakistan Academy of Sciences.
  • 2000: Foreign Fellow of Pakistan Academy of Sciences.
  • 1997 - 2003: Vice President Third World Academy of Sciences.
  • 1996: Third World Academy of Sciences Medal Lecturer.
  • 1993: Royal Society of Chemistry Flintoff Medal.
  • 1992 - 1997: Treasurer & Member of Council of Third World Academy of Sciences.
  • 1984: Founding Fellow of the Third World Academy of Sciences.
  • 1983 - 1985: Member of the Council of the Royal Society.
  • 1981: Sitara-I-Imtiaz, Government of Pakistan.
  • 1980: Fellow of the Royal Society, UK.
Professor Muhammad Akhtar
Biological Sciences Building 85 University of Southampton Highfield Campus Southampton SO17 1BJ E-mail: ma3@soton.ac.uk

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