Abstract

We are studying the effect of ?-6 amino acid on the ? and ? assembly to produce tetrameric hemoglobin using time resolved spectroscopy. Hb S usually comprises about 40% of the total hemoglobin in the red cells of individuals with sickle cell trait. This lesser amount of Hb S compared to Hb A in persons with sickle cell trait, having a full complement of alpha genes is puzzling. In vitro ? and ? mixing experiments show that ?-? A dimers form more readily than the S dimer. The reasons for this are not readily apparent. The ?-6 amino acid is on the surface of the ? chain and far removed from the ?-1?-1 contact region that is critical for the initial formation of ??? dimers. We are now able to systematically test the effects of ?-6 amino acid charge and hydrophobicity on assembly of hemoglobin molecules by engineering various mutations at the ?-6 position. These studies will be important for understanding reasons for higher levels of the Hb S in sickle cell compared t o A type red cells. Furthermore, this difference is an important determinant of the clinical manifestations of sickle cell disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001348-18
Application #
6120153
Study Section
Project Start
1999-08-01
Project End
2000-07-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
18
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Sheth, Rahul A; Arellano, Ronald S; Uppot, Raul N et al. (2015) Prospective trial with optical molecular imaging for percutaneous interventions in focal hepatic lesions. Radiology 274:917-26
Roussakis, Emmanuel; Spencer, Joel A; Lin, Charles P et al. (2014) Two-photon antenna-core oxygen probe with enhanced performance. Anal Chem 86:5937-45
Courter, Joel R; Abdo, Mohannad; Brown, Stephen P et al. (2014) The design and synthesis of alanine-rich ?-helical peptides constrained by an S,S-tetrazine photochemical trigger: a fragment union approach. J Org Chem 79:759-68
Singh, Prabhat K; Kuroda, Daniel G; Hochstrasser, Robin M (2013) An ion's perspective on the molecular motions of nanoconfined water: a two-dimensional infrared spectroscopy study. J Phys Chem B 117:9775-84
Chuntonov, Lev; Ma, Jianqiang (2013) Quantum process tomography quantifies coherence transfer dynamics in vibrational exciton. J Phys Chem B 117:13631-8
Culik, Robert M; Annavarapu, Srinivas; Nanda, Vikas et al. (2013) Using D-Amino Acids to Delineate the Mechanism of Protein Folding: Application to Trp-cage. Chem Phys 422:
Kuroda, Daniel G; Bauman, Joseph D; Challa, J Reddy et al. (2013) Snapshot of the equilibrium dynamics of a drug bound to HIV-1 reverse transcriptase. Nat Chem 5:174-81
Lam, A R; Moran, S D; Preketes, N K et al. (2013) Study of the ?D-crystallin protein using two-dimensional infrared (2DIR) spectroscopy: experiment and simulation. J Phys Chem B 117:15436-43
Kuroda, Daniel G; Singh, Prabhat K; Hochstrasser, Robin M (2013) Differential hydration of tricyanomethanide observed by time resolved vibrational spectroscopy. J Phys Chem B 117:4354-64
Goldberg, Jacob M; Speight, Lee C; Fegley, Mark W et al. (2012) Minimalist probes for studying protein dynamics: thioamide quenching of selectively excitable fluorescent amino acids. J Am Chem Soc 134:6088-91

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