Sequence-specific sup 1 H NMR assignments, secondary structure, and location of the calcium binding site in the first epidermal growth factor like domain of blood coagulation factor IX

Journal Article · Tue Jul 30 00:00:00 EDT 1991 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00244a006· OSTI ID:5025416

Huang, L H; Cheng, H; Sweeney, W V ^[1]; Pardi, A ^[2]; Tam, J P ^[3]

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1. Hunter Coll., New York, NY (United States)
2. Univ. of Colorado, Boulder (United States)
3. Rockefeller Univ., New York, NY (United States)

Factor IX is a blood clotting protein that contains three regions, including a {gamma}-carboxyglutamic acid (Gla) domain, two tandemly connected epidermal growth factor like (EGF-like) domains, and a serine protease region. The protein exhibits a high-affinity calcium binding site in the first EGF0like domain, in addition to calcium binding in the Gla domain. The first EGF-like domain, factor IX (45-87), has been synthesized. Sequence-specific resonance assignment of the peptide has been made by using 2D NMR techniques, and its secondary structure has been determined. The protein is found to have two antiparallel {beta}-sheets, and preliminary distance geometry calculations indicate that the protein has two domains, separated by Trp{sup 28}, with the overall structure being similar to that of EGF. An NMR investigation of the calcium-bound first EGF-like domain indicates the presence and location of a calcium binding site involving residues on both strands of one of the {beta}-sheets as well as the N-terminal region of the peptide. These results suggest that calcium binding in the first EGF-like domain could induce long-range (possibly interdomain) conformational changes in factor IX, rather than causing structural alterations in the EGF-like domain itself.

• OSTI ID: 5025416
• Journal Information: Biochemistry; (United States), Vol. 30:30; ISSN 0006-2960
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
BLOOD COAGULATION FACTORS
NUCLEAR MAGNETIC RESONANCE
GROWTH FACTORS
MOLECULAR STRUCTURE
CALCIUM COMPOUNDS
CHEMICAL SHIFT
EPIDERMIS
HEAVY WATER
MAN
ALKALINE EARTH METAL COMPOUNDS
ANIMAL TISSUES
ANIMALS
BODY
COAGULANTS
DRUGS
EPITHELIUM
HEMATOLOGIC AGENTS
HYDROGEN COMPOUNDS
MAGNETIC RESONANCE
MAMMALS
MITOGENS
ORGANIC COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PRIMATES
PROTEINS
RESONANCE
SKIN
TISSUES
VERTEBRATES
WATER
550201* - Biochemistry- Tracer Techniques