1VWT

T STATE HUMAN HEMOGLOBIN [ALPHA V96W], ALPHA AQUOMET, BETA DEOXY

Summary for 1VWT

• Entry DOI: 10.2210/pdb1vwt/pdb
• Descriptor: HEMOGLOBIN, PROTOPORPHYRIN IX CONTAINING FE, SULFATE ION, ... (5 entities in total)
• Functional Keywords: oxygen transport, hemoglobin, human, mutant, alpha-(v96w), deoxy, deoxy hemoglobin, met hemoglobin
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 64913.34

Authors

Puius, Y.A.,Zou, M.,Ho, N.T.,Ho, C.,Almo, S.C. (deposition date: 1997-03-20, release date: 1998-03-25, Last modification date: 2024-05-22)

Primary citation

Puius, Y.A.,Zou, M.,Ho, N.T.,Ho, C.,Almo, S.C.
Novel water-mediated hydrogen bonds as the structural basis for the low oxygen affinity of the blood substitute candidate rHb(alpha 96Val-->Trp).
Biochemistry, 37:9258-9265, 1998

PubMed Abstract: 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.

PubMed: 9649306
DOI: 10.1021/bi9727287

Experimental method

X-RAY DIFFRACTION (1.9 Å)