1vwt
|
T STATE HUMAN HEMOGLOBIN [ALPHA V96W], ALPHA AQUOMET, BETA DEOXY
OverviewOverview
One of the most promising approaches for the development of a synthetic, blood substitute has been the engineering of novel mutants of human, hemoglobin (Hb) A which maintain cooperativity, but possess lowered oxygen, affinity. We describe here two crystal structures of one such potential, blood substitute, recombinant (r) Hb(alpha 96Val-->Trp), refined to 1.9 A, resolution in an alpha-aquomet, beta-deoxy T-state, and to 2.5 A, resolution in a carbonmonoxy R-state. On the basis of molecular dynamics, simulations, a particular conformation had been predicted for the, engineered Trp residue, and the lowered oxygen affinity had been, attributed to a stabilization of the deoxy T-state interface by alpha, 96Trp-beta 99Asp hydrogen bonds. Difference Fourier maps of the T-state, structure clearly show that alpha 96Trp is in a conformation different, from that predicted by the simulation, with its indole side chain directed, away from the interface and into the central cavity. In this conformation, the indole nitrogen makes novel water-mediated hydrogen bonds across the, T-state interface with beta 101Glu. We propose that these water-mediated, hydrogen bonds are the structural basis for the lowered oxygen affinity of, rHb(alpha 96Val-->Trp), and discuss the implications of these findings for, future molecular dynamics studies and the design of Hb mutants.
About this StructureAbout this Structure
1VWT is a Protein complex structure of sequences from Homo sapiens with SO4 and HEM as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Novel water-mediated hydrogen bonds as the structural basis for the low oxygen affinity of the blood substitute candidate rHb(alpha 96Val-->Trp)., Puius YA, Zou M, Ho NT, Ho C, Almo SC, Biochemistry. 1998 Jun 30;37(26):9258-65. PMID:9649306
Page seeded by OCA on Thu Nov 8 13:20:10 2007