Guided by wikipedia and pmc I found this paper by Hamilton O. Smith. and .Daniel Nathans.

A restriction enzyme is a component of a restriction-modification system of a given specificity within an organism. The R-MT system consists of two enzymatic components, a restriction endonuclease, and a modification enzyme sharing similar (or identical) recognition specificity. We would like to propose that the genus-species designation be used as an R-M system name according to the following rules.

(1) The genus and species name of the host organism is identified by the first letter of the genus and the first two letters of the species to form a three-letter abbre- viation in italics. For example: E. coli, Eco and H. influenzae, Hin.

(2) Strain or type identification follows the genus-species abbreviation in non- italicized symbols, e.g. EcoB or EcoK. In cases where the R-M system is genetically specified by a virus or pla,smid the italicized genus-species abbreviation of the host is given and the symbol for the extrachromosomal element follows in non-italics, e.g. EcoPl, EwRI, etc. In occasional cases where it might be necessary to specify the host strain as well as the extrachromosomal element the strain identification symbol may be inserted parenthetically, e.g. Eco(B)Pl.

(3) When a particular host strain has several different R-M systems, these are identified by Roman numerals, thus, the R-M systems from H. injluenzae strain d would be HindI, HindII, HindIII, etc.

Main question:

Now HindII was -

  1. extracted from Haemophilus influenzae
  2. the strain was strain Rd, so d
  3. and it was the 2nd enzyme to be isolated? Hence II.

So how is it the first Type II RE?

H.O. Smith, K.W. Wilcox, and T.J. Kelley, working at Johns Hopkins University in 1968, isolated and characterized the first restriction nuclease whose functioning depended on a specific DNA nucleotide sequence. (wiki)

  • 2
    $\begingroup$ I don't know how widely this has been accepted but Roberts proposed in 2003 that the italics should be dropped (ncbi.nlm.nih.gov/pmc/articles/PMC152790). I used to be a stickler for using italics, but I now prefer without. $\endgroup$ – Alan Boyd May 9 '17 at 14:57
  • $\begingroup$ I'm voting to close this question as off-topic because it's not about biology it's about history, and not very interesting history either. Why should you care whether it was HindIII or EcoRI for goodness sake! $\endgroup$ – David May 9 '17 at 18:17
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    $\begingroup$ I don't understand what can be wrong in getting a doubt cleared? The question (in the title which still stands unedited) was the main question behind this post. NCERT (a book back from my school) did not mention the Type II part to keep things simple. It lingered in my mind (as why an enzyme which is II yet the first) and definitely it was my silly mistake to not have observed the Type II thing even while reading it after so many years. My question wasn't which one's the 1st enzyme? But why HindII the first one? @David $\endgroup$ – Tyto alba May 9 '17 at 18:41
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    $\begingroup$ I call them as I see them. (Friendly tip: best to try to avoid Indian English "doubt" on International forums — use "question" instead.) $\endgroup$ – David May 9 '17 at 18:51
  • $\begingroup$ if the strain is Rd then instead of Hind,HinR should have been written, what is the answer $\endgroup$ – Jayakumar Aug 10 '17 at 14:25

The explanation here is quite simple: HindI, despite having been isolated/discovered before HindII, is a type I Restriction Enzyme, not a type II:

A type I restriction enzyme from Haemophilus influenzae, Hind I, which requires adenosine 5'-triphosphate and 5-adenosyl methionine, was studied for its activity on transfecting and transforming deoxyribonucleic acid (DNA) [...] Most of the restriction enzymes from Haemophilus belong to type II restriction enzymes according to the classification system proposed by Boyer. These enzymes require only Mg2+ for their action in contrast to type I enzymes that require Mg2+, adenosine 5'-triphosphate (ATP), and S-adenosyl methionine (SAM).

(Source: Biological Properties of a Haemophilus influenzae Restriction Enzyme, Hind I)

Thus, in fact, HindII was the first type II Restriction Enzyme isolated/discovered, as it's well documented.

PS: As a bonus, here is a table with the main differences among RE types I, II, III and IV (Source: Thermo Fisher Scientific):

Type I:

  • Multi-subunit protein with both restriction and methylation activities
  • ATP requirement
  • Cleavage site a variable distance from recognition site

Type II:

  • Specific recognition sequence
  • Cleavage site within or close to recognition sequence
  • Generates 5′ phosphate and 3′ hydroxyl termini at cleavage site
  • Mg2+ requirement for most

Type III:

  • Two-part recognition sequence in inverse orientation
  • Cleavage site a specific distance away from one of the recognition sequences
  • ATP requirement

Type IV:

  • Cleavage of only methylated DNA
  • Cleavage site approximately 30 base pairs away from recognition site

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