1DQB

NMR STRUCTURE OF THROMBOMODULIN EGF(4-5)

Summary for 1DQB

• Entry DOI: 10.2210/pdb1dqb/pdb
• Related: 1adx 1zaq 2adx
• NMR Information: BMRB: 4630
• Descriptor: THROMBOMODULIN, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• Functional Keywords: thrombin, egf module, anticoagulant, glycosylation, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 9742.77

Authors

Wood, M.J.,Sampoli-Benitez, B.A.,Komives, E.A. (deposition date: 2000-01-03, release date: 2000-03-06, Last modification date: 2024-10-16)

Primary citation

Wood, M.J.,Sampoli-Benitez, B.A.,Komives, E.A.
Solution structure of the smallest cofactor-active fragment of thrombomodulin.
Nat.Struct.Biol., 7:200-204, 2000

PubMed Abstract: A glycosylated fragment of thrombomodulin containing two epidermal growth factor-like domains (TMEGF45) was analyzed by NMR. The 4th-domains structure of this two-domain fragment is similar to that of the individual domain previously determined. The 5th-domain, which has uncrossed disulfide bonds, is not as well determined in the two-domain fragment than the individual domain previously solved. The flexibility of the 5th-domain is consistent with low heteronuclear NOEs. In the individual 5th-domain, Met 388 was disordered, and key thrombin binding residues formed a hydrophobic core. By contrast, in TMEGF45, Met 388 is in the 5th-domain core, positioned by Phe 376 from the 4th-domain. As a result, key thrombin binding residues that were in the core of the individual domain are expelled. Upon thrombin binding, chemical shifts of two residues in the 4th-domain, the three interdomain linker residues, and nearly all of the 5th-domain are perturbed. Thus, TMEGF45 binds thrombin by an induced fit mechanism involving a flexible 5th-domain.

PubMed: 10700277
DOI: 10.1038/73302

Experimental method

SOLUTION NMR